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Journal of Experimental Botany, Vol. 66, No. 6 pp. 1661–1671, 2015
doi:10.1093/jxb/erv022 Advance Access publication 19 February 2015
Review Paper
Exploring the pleiotropy of hos1
Dana R. MacGregor* and Steven Penfield
John Innes Centre, Department of Crop Genetics, Norwich Research Park, Colney Lane, Norwich, Norfolk NR4 7UH, UK
* To whom correspondence should be addressed. E-mail: [email protected]
Received 14 November 2014; Revised 19 December 2014; Accepted 23 December 2014
Abstract
Understanding of the roles that HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 1 (HOS1) plays in the
plant’s ability to sense and respond to environmental signals has grown dramatically. Mechanisms through which
HOS1 affects plant development have been uncovered, and the broader consequences of hos1 on the plant’s ability
to perceive and respond to its environment have been investigated. As such, it has been possible to place HOS1 as a
key integrator of temperature information in response to both acute signals and cues that indicate time of year into
developmental processes that are essential for plant survival. This review summarizes knowledge of HOS1’s form
and function, and contextualizes this information so that it is relevant for better understanding the processes of cold
signalling, flowering time, and nuclear pore complex function more broadly.
Key words: Circadian clock, cold signalling, flowering time, HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 1
(HOS1), mRNA export, nuclear pore.
Introduction
Being able to recognize a rapid reduction in temperature and
respond appropriately allows a plant to survive in variable
environments with freezing temperatures. Likewise, it is particularly important for annual plants to be able to correctly
interpret seasonal cues, such as day-length and changing
trends in average temperature, so that flowering and seed set
occur only at the right time of year. The genes and proteins
involved in the response to cold and control of flowering time
are under the control of the circadian clock, which ensures
that the appropriate timing and level of response occurs.
HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE
GENE 1 (HOS1) plays a role in circadian function, but is also
a negative regulator of both cold signalling and flowering
time, and is therefore a candidate integrator of environmental information into signalling events that are necessary for
plant survival. At the molecular level, HOS1 accomplishes
these functions by working as part of the Nuclear Pore
Complex (NPC), where it is involved in the regulation of protein and mRNA levels through various mechanisms. HOS1
is therefore important for the plant’s ability to adapt to an
ever-changing environment. This review investigates the various mechanisms in which HOS1 is able to accomplish these
functions while pointing out connections, complexities, and
outstanding questions.
HOS1 is conserved within plants and is
alternately spliced
HOS1 is encoded by the Arabidopsis thaliana gene At2g39810,
and the HOS1 locus gives rise to two splice isoforms, HOS1-L
and HOS1-S (Fig. 1A; Ishitani et al., 1998; Lee et al. 2012b).
The alternative splicing of HOS1 means that HOS1-L includes
12 additional amino acid residues, as the HOS1-S start site is
within the first intron of HOS1-L (Fig. 1B). This 12 amino
acid difference is upstream of the known functional and conserved domains and is upstream of the hos1-1, hos1-2, hos1-3,
hos1-5, and hos1-6 mutations (Lee et al., 2001; Lazaro et al.,
2012; MacGregor et al., 2013). It is unclear if the location of
the hos1-4 mutation (Lazaro et al., 2012) is contained in both
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1662 | MacGregor and Penfield
isoforms, as the splice variant used to describe the position
of this point mutation was not defined. When putative HOS1
sequences from multiple plant species are compared, the protein sequence of A. thaliana HOS1-L is more highly conserved
compared to HOS1-S, and is nearly identical to the predicted
HOS1 protein sequences from A. lyrata and Thellungiella
halophila (Lee et al., 2012b). Characterization of the different splice variants showed them to be broadly similar in their
expression patterns and their ability to interact with a known
ubiquitination target (Lee et al., 2012b). There are two notable differences in these isoforms: (i) HOS1-L is expressed at
a higher level than HOS1-S; and (ii) when plants are treated
with a transient cold shock, there is a rapid and transient
reduction of expression of both splice variants, but the recovery of HOS1-S to pre-cold levels occurs more rapidly than
HOS1-L (Lee et al., 2012b). Interestingly, early characterization of HOS1 also described the HOS1-S isoform as well
as this rapid, transient reduction in HOS1 mRNA levels in
response to a cold shock (Lee et al., 2001). This rapid removal
of HOS1 mRNA is suggested to then alleviate the repressive
effects of the HOS1 protein, thereby permitting a transient
response to the environmental stimuli (see ‘HOS1 Negatively
Regulates Cold Signalling’; Lee et al., 2001; Lee et al., 2012b).
As these two isoforms appear to be largely similar in
expression patterns and function (Lee et al., 2012b), and most
studies do not define which isoform they analyse, they are
not differentiated in the remainder of this review. However,
both isoforms do exist in planta and there is evidence that
they play slightly different roles in the regulation of flowering time (see ‘HOS1 Negatively Regulates the Transition
to Flowering’, Lee et al, 2012b). It would be interesting to
extend this comparative analysis beyond flowering time regulation and re-evaluate the other known functions of HOS1
with the aim of determining where, if at all, the resulting
proteins differ.
Sequences encoding putative HOS1 from other plant species have also been found and the overall level of conservation
is good (Lee et al., 2012b). OsHOS1 from Oryza sativa is 49%
identical to AtHOS1 at the amino acid sequence level, and
it also performs many of the same functions as AtHOS1 in
modulating cold signalling (Lourenço et al., 2013; see ‘HOS1
Negatively Regulates Cold Signalling’). As HOS1 is an
important coordinator of several environmental inputs into
fundamental developmental processes, it would be interesting to investigate whether this sequence conservation among
plants translates into conservation of function across the
species beyond just Arabidopsis and rice, as well as extending the analysis to determine if the other roles of HOS1 are
conserved.
The hos1 mutant is highly pleiotropic
hos1 mutants have been shown to disrupt many plant processes. For instance, HOS1 has been identified in screens for
altered cold stress responses, early flowering under various
different conditions, altered circadian rhythms, and in a proteomic study for components of the nuclear pore (Ishitani et al.,
1998; Tamura et al., 2010; Lazaro et al., 2012; MacGregor
et al., 2013). One difficulty in unpicking the mechanisms of
HOS1 action is that many of these pathways are intricately
interconnected. For instance, intermittent cold temperatures
delay flowering (Seo et al., 2009), and elements of the chromatin remodelling machinery that act on the flowering time
pathway genes are also required for freezing tolerance and
cold signalling (To et al., 2011b). The protein modifier SIZ1
acts to regulate protein stability of transcription factors key
to both cold signalling and the flowering time pathway (Miura
et al., 2007; Jin et al., 2008). The external coincidence model
uses the clock to correctly coordinate flowering time with day
length (Carré, 2001). Nuclear pore function is required for
correct circadian periodicity (MacGregor et al., 2013) and
flowering time (Parry, 2014). The circadian clock is not only
entrained by temperature fluctuations (Eckardt, 2005), but
Fig. 1. The structure of HOS1. (A) Genomic structure of both splice variants of HOS1 (At2g39810) showing exons (grey boxes) and introns (black
lines). Figure based on The Arabidopsis Information Resource (TAIR), http://www.arabidopsis.org/servlets/TairObject?id=35204&type=locus. (B) Protein
structure of both splice variants of HOS1 showing RING domain (yellow box), homology to Elys (blue dotted box), NLS (green box), and sequence of
uncharacterized structure (red boxes). The C-terminal portion of the protein that is important for protein–protein interactions has been identified with a
bracket. Figure based on Lee et al., 2012b. (C) Structural comparison between A. thaliana HOS1 from Fig. 1B with Homo sapiens Elys. The Elys structures
identified are the region of homology (blue dotted box), the β-propeller domain (orange box), the central α-helical domain (purple box), the DNA-binding
domain (pink box), and the C-terminal disordered region (brown box). Figure based on Tamura et al., 2010 and Bilokapic and Schwartz, 2013.
Exploring the pleiotropy of hos1 | 1663
the components and correct functioning of the clock itself
play an important role in gating temperature signal transduction (Thomashow, 2010; Keily et al., 2013). Therefore,
although it is common to compartmentalize phenotypes and
functions within one pathway or another, it is important to
consider that these signalling pathways do not work in isolation but are tightly connected. Therefore, future research on
HOS1 and other nuclear pore proteins would benefit from
considering whether the phenotype being studied is a direct
consequence of the mutation or an indirect effect acting
through one of these other interconnected pathways.
To understand what it is that HOS1 does, it is important to
consider what HOS1 encodes. The HOS1 sequence encodes
for a protein of 927 (HOS1-L) or 915 (HOS1-S) amino acids.
As shown in Fig. 1B, both splice isoforms of the protein
have a variant C3HC4 Really Interesting New Gene (RING)
finger E3 ligase domain, followed by a region of homology to the vertebrate nucleoporin EMBRYONIC LARGE
MOLECULE DERIVED FROM YOLK SAC (Elys), and
a nuclear localization signal (NLS) (Lee et al., 2001; Dong
et al., 2006a; Tamura et al., 2010). Of these, only the RING
domain has been demonstrated to be necessary but not sufficient for E3 ligase activity of HOS1, as demonstrated by
in vitro ubiquitination assays using HOS1, truncated HOS1
mutants, or point mutations in HOS1 altering conserved histidine or cytosine residues (Dong et al., 2006a); however the
E3 ligase activity of these variants or their ability to rescue
the loss of HOS1 have not been reported in vivo. Much of
the rest of the protein is uncharacterized, does not contain
sequences common to domains of known function, and only
has sequence similarity to other plant genomes.
The final 11 amino acids of the HOS1 sequence are a
putative NLS (Fig. 1B), but there are no reports demonstrating that this sequence is required for HOS1 localization. Analysis of HOS1 promoter activity demonstrated that
HOS1 is expressed ubiquitously throughout the plant (Lee
et al., 2001). Within the cell, Lee et al. (2001) and Lee et al.
(2012a) show nucleo-cytoplasmic partitioning of the HOS1
protein: under ambient temperatures, HOS1 is predominantly cytoplasmic, but it concentrates in the nucleus after
a shift to cold temperatures. HOS1 has also been localized
at the nuclear envelope, specifically as a component of the
NPC, at ambient temperature or at all temperatures tested,
and in both light and dark conditions (Tamura et al., 2010;
Lazaro et al., 2012; MacGregor et al., 2013). The human
nucleoporin Nup98 is mobile, dynamically associating with
the NPC as well as being localized in both the nucleus and the
cytoplasm (Zolotukhin and Felber, 1999; Griffis et al., 2002;
Griffis et al., 2004). Therefore, there is a precedent for mobile
nuclear pore components, and the movement of HOS1 may
be important for its ability to regulate downstream processes.
As HOS1 has been characterized as an E3 ligase (Dong et al.,
2006a), a component of the nuclear pore (Tamura et al.,
2010), and finally a chromatin remodelling factor (Jung et al.,
2013), it is clear that the localization of HOS1 is vital for its
ability to interact with partners and regulate signalling events
as sequestration in one compartment of the cell would limit
access to its partners.
HOS1 is a component of the nuclear pore
and is required for mRNA export
Tamura et al. (2010) performed a series of interaction studies to identify components of the Arabidopsis NPC, using the
conserved core components of the outer ring of the nuclear
pore RNA EXPORT FACTOR 1 (RAE1) and Nup43 as
baits (Fig. 2). HOS1 interacted with both RAE1 and Nup43,
and has a region of sequence similarity to the vertebrate
nucleoporin Elys, lending further support to the association
of HOS1 with the NPC (Fig. 1) (Tamura et al., 2010). Elys
is a dual nucleoporin/kinetochore protein, and Elys and its
homologue MATERNAL EFFECT LETHAL-28 (Mel-28)
in Caenorhabditis elegans are required for the correct assembly of the nuclear pores, a functional nuclear envelope, and
the formation of subdomains within the nuclear envelope
after mitosis (Galy et al., 2006; Rasala et al., 2006; Clever
et al., 2012). Analysis of the Elys protein has demonstrated
that it is made up of three domains: (i) an N-terminal
β-propeller domain, (ii) a central α-helical domain, and (iii)
a C-terminal disordered region (Fig. 1C) (Bilokapic and
Schwartz, 2013). The first two domains contain the region of
homology to HOS1, and synergistically mediate tethering to
the NPC, while the disordered region is responsible for the
interactions with chromatin (Bilokapic and Schwartz, 2013).
However, the region of homology between HOS1 and Elys is
a small portion of both proteins (Fig. 1C), and otherwise the
protein sequences of Elys and HOS1 are not well conserved.
Therefore caution is required when extrapolating protein
function from Elys to HOS1.
Two groups have independently demonstrated HOS1 is
localized to the nuclear envelope using florescent protein
fusions (Lazaro et al., 2012; MacGregor et al., 2013); however, the resolution of these images is insufficient to determine
whether HOS1 is restricted to the NPC or if it is positioned
on the cytoplasmic and/or nucleoplasmic side of the envelope.
We cannot predict which side of the pore HOS1 is located
because the components with which it interacts are located on
both sides of the nuclear envelope (Fig. 2), and Elys has not
been positioned on one side or another. However, as HOS1
interacts with chromatin (Jung et al., 2013), it is likely that
it is located at least on the nucleoplasmic side of the NPC, if
not free in the nucleus.
HOS1 is not only located at the NPC, but is also required
for the basic NPC function of mRNA export (MacGregor
et al., 2013). mRNA is transcribed in the nucleus and then
transported to the cytoplasm via the NPC. Mutations to the
NPC, including hos1, alter this process leading to an accumulation of polyA-containing mRNA in the nucleus (Dong
et al., 2006b; Parry et al., 2006; Xu et al., 2007; Lu et al., 2010;
Wiermer et al., 2012; MacGregor et al., 2013; Parry, 2014).
Withholding mRNA in the nucleus is likely to have many deleterious effects, and one that has recently been identified is that
mRNA retention leads to a long period of the circadian clock
(MacGregor et al., 2013). The Arabidopsis circadian clock is
composed of three interlocking transcription-translational
feedback loops which are responsive to both temperature and
light but also compensated against these changes so that the
1664 | MacGregor and Penfield
Fig. 2. Components of the nuclear pore complex and their localization within the pore. Rectangles indicate structures that are composed of multiple
proteins, and circles, individual proteins; HOS1 is highlighted as a ten-point star. The HOS1-interacting proteins RAE1 and Nup43 are underlined. The
tables at the top indicate where loss of function of that gene leads to the indicated phenotype. The colour coding indicates the position within the pore:
green, cytoplasmic ring and filaments; orange, central pore proteins; red, transmembrane or membrane-associated proteins; blue, nuclear linker or
nuclear basket proteins; yellow, central scaffolding proteins. The pink curved line represents the nuclear membrane. The structure of the nuclear pore is
compiled based on figures in Parry (2014) and Tamura et al. (2010) overlaid on Fig. 1 of Raices and D’Angelo (2012).
clock consistently runs with a 24-hour period (Pokhilko et al.,
2012; Gould et al., 2013). It is known that altering the amounts
of any one of the clock components can lead to changes in
period length (McClung, 2006); however, analysis of double
mutants between hos1 and clock components did not provide evidence for a genetic interaction between HOS1 and
these components of the circadian clock (MacGregor et al.,
2013). hos1 does result in lowered protein levels of the core
circadian component LATE ELONGATED HYPOCOTYL
(LHY) but does not alter its rhythm (MacGregor et al.,
2013). Therefore, a simplistic model for how hos1 and the
other NPC mutants tested change circadian period is that
when mRNA export is reduced, it results in changes to the
protein amounts of many if not all of the clock components,
and these changes collectively lead to a lengthening of the
period. The role of HOS1 in the maintenance of circadian
periodicity is unique, as unlike the other hos1 phenotypes, the
hos1 clock has a long period under all temperature and light
regimes tested, and therefore does not appear to have a temperature or light dependency (MacGregor et al., 2013).
HOS1 acts as a negative regulator through
protein–protein or protein–chromatin
interactions
The C-terminal portion of the HOS1 protein (Fig. 1B) is
important for protein–protein interactions. The region from
Exploring the pleiotropy of hos1 | 1665
approximately amino acid 450 either to the end of the protein, or to the NLS, has been used to demonstrate that HOS1
interacts with INDUCER OF CBF EXPRESSION 1 (ICE1,
also known as SCREAM), FVE, FLOWERING LOCUS
KH DOMAIN (FLK), CONSTANS (CO), and several histone deacetylases such as HISTONE DEACETYLASE 6
(HDA6) and HDA15 (Dong et al., 2006a; Jung et al., 2012;
Lee et al., 2012a; Jung et al., 2013) (Fig. 3). Interestingly, for
many of these in vitro interactions, such as the interaction
with ICE1 or CO, the full-length protein does not appear to
interact as strongly with its partners as does the truncated
version (Dong et al., 2006a; Jung et al., 2012). There are many
possible reasons, both biological and technical, why fulllength HOS1 does not interact as well as the truncated version. For instance, it is possible that expression of full-length
HOS1 in the heterologous system results in a protein structure that is less accessible for interactions because it requires
additional post-translational modifications or interacting
partners not present in yeast. Also, the yeast two-hybrid system may require that the interactions occur at an abnormal
subcellular localization for the full-length protein. The region
of HOS1 that is deleted to make the truncated HOS1 contains the region of Elys homology, and in Elys this region is
contained within the portion of the protein known to mediate
tethering to the NPC (Fig. 1) (Bilokapic and Schwartz, 2013).
It is also possible that interaction with full-length HOS1 protein results in ubiquitination and degradation of the target,
and therefore the interaction cannot be observed because the
signal for interaction is not being properly propagated. The
interactions identified using the truncated HOS1 are occurring in planta as demonstrated by additional techniques such
as in vivo pull-down assays and bimolecular fluorescence
complementation (BiFC) approaches. Additional work needs
to be done to determine whether the observed differences in
the strength of interaction between the full-length and truncated HOS1 are biologically relevant or artefacts of the testing systems.
Every protein–protein interaction in which HOS1 participates does not necessarily result in ubiquitination and protein degradation. To regulate cold signalling or flowering
time, HOS1 acts to regulate the protein levels of ICE1 or
CO, respectively, and is both necessary and sufficient to alter
their ubiquitination levels (see below). However, HOS1 also
interacts with several other proteins, and for these there is no
evidence that the HOS1 interaction leads to ubiquitination or
changes in protein levels. For instance, Lee et al. (2012a) were
unable to demonstrate ubiquitination of FVE by HOS1 in
vitro. Likewise, although HOS1 interacts with HDA6 and the
ability of HDA6 to bind to the promoter of FLC is altered
by levels of HOS1, amounts of HDA6 protein are not altered
with cold and no ubiquitination of HDA6 was observed in
the presence of HOS1 (Jung et al., 2013). Therefore, HOS1 is
required to serve some additional functions in addition to its
role as an E3 ubiquitin ligase.
HOS1 negatively regulates cold signalling
HOS1 was originally isolated in a screen for mutations that
altered the expression of a cold- and osmotic stress-responsive
promoter driving LUCIFERASE expression (RD29A:LUC;
Ishitani et al., 1998). As its name HIGH EXPRESSION OF
OSMOTICALLY RESPONSIVE GENE 1 implies, hos1-1
led to increased RD29A:LUC luminescence when plants were
exposed to cold, but there was no significant luminescence in
the absence of treatment or between the wild type and hos1-1
treated with abscisic acid (ABA) or salt (NaCl). hos1 led to
Fig. 3. Illustration of HOS1 interactions and downstream signalling events important for circadian periodicity, cold signalling, and flowering time. The
purple boxes are E3 ubiquitin ligases, the yellow boxes are transcription factors, the orange box is a SUMO modifier, the blue box is an SPA family
member, the green boxes are chromatin remodelling factors, and the grey clocks represent the circadian clock. The red rectangles indicate promoters
with the known binding sites indicated, and the dark green rectangle indicates the chromatin remodelling that occurs at the promoter of FLC. The linked
purple circles represent poly-ubiquitination events of ICE1 and CO by HOS1 or CO by COP1; the 26S proteasome is drawn in cartoon. Linked orange
circles represent SUMOylation of ICE1 by SIZ1. Arrows indicate promotion and T-junctions indicate inhibition. Double-lined arrows indicate indirect
effects, and single lined arrows indicate direct effects.
1666 | MacGregor and Penfield
an increased cold response over a large range of temperatures
where, importantly, the wild type shows no luminescence
above 10°C yet hos1-1 luminesced up to 19°C (Ishitani et al.,
1998). HOS1 is also necessary and sufficient for the normal
expression of many additional cold-responsive and coldsignalling genes (Ishitani et al., 1998; Lee et al., 2001; Dong
et al., 2006a; Lourenço et al., 2013; MacGregor et al., 2013).
There appear to be at least two mechanisms through which
HOS1 is altering cold gene expression: through modulation
of ICE1 protein levels and by regulating mRNA export.
INDUCER OF CBF EXPRESSION 1 (ICE1) is a basic
helix-loop-helix transcription factor that interacts with DNA
as well as several proteins and is important for cold signalling (Chinnusamy et al., 2003; Lee et al., 2005; Miura et al.,
2007; Miura et al., 2011; Hu et al., 2013), stomatal development and patterning (Kanaoka et al., 2008), temperature-regulated pathogen resistance (Zhu et al., 2011), and endosperm
breakdown during seed development (Denay et al., 2014).
During cold signalling ICE1 acts to control expression of
the C-REPEAT/DRE BINDING FACTOR (CBF) family of
transcription factors through binding to the CBF3 promoter,
initiating a signalling cascade that is necessary for tolerance
to cold stress (Fig. 3) (Chinnusamy et al., 2003; Lee et al.,
2005; Miura et al., 2007; Miura et al., 2011; Hu et al., 2013).
ICE1 is widely conserved among higher plants (Kurbidaeva
et al., 2014), and for several ICE1 orthologues there is functional evidence that ICE1 is also necessary and/or sufficient
to regulate cold-stress responses (Badawi et al., 2008; Chen
et al., 2012; Wang et al., 2012; Chen et al., 2013; Dong et al.,
2013; Feng et al., 2013; Zhao et al., 2013; Shan et al., 2014;
Xu et al., 2014). The HOS1–ICE1 interaction is necessary for
the polyubiquitination of ICE1 and its subsequent degradation by the proteasome; amounts of ICE1 protein are correlated with levels of CBF and other cold-responsive gene
expression (Dong et al., 2006a; Lee et al., 2012b; Lourenço
et al., 2013). The proposed mechanism for HOS1 regulation
of ICE1 is that under ambient temperatures, HOS1 ensures
that ICE1 levels are low and the cold signalling pathway is
not induced. In response to a short pulse of cold, the level
of HOS1 mRNA rapidly and transiently decreases, implying
that HOS1 protein levels are reduced; removal of the HOS1
protein alleviates ICE1 degradation, allowing ICE1 to initiate cold responses through CBF3 (Lee et al., 2001; Lee et al.,
2012b). Also, in response to a reduction of temperature,
HOS1 moves from a predominantly cytoplasmic localization
into the nucleus (Lee et al., 2001; Lee et al., 2012a), where
it is able to interact with and target ICE1 for degradation,
ensuring that the induction of cold responses is transient.
To balance HOS1-mediated degradation, ICE1 is also posttranslationally modified by SIZ1, which stabilizes it through
the addition of SUMO modifications (Fig. 3) (Miura et al.,
2007). Therefore, by regulating ICE1 protein levels through
ubiquitination, as balanced by SUMOylation, HOS1 can
modulate an appropriate response to transient cold. Further
work is required to understand how these transient responses
relate to the plant’s ability to survive temperature changes
that occur under more natural conditions.
Other than this transient response to cold, there is little evidence for transcriptional regulation of HOS1, as shown by
analysis of HOS1 in the wild type under various conditions
and treatments. HOS1 is ubiquitously expressed throughout
the plant and, excluding the rapid response to temperature
explained above, its expression is not significantly altered by
growing the plants at various temperatures or in response
to treatments such as exogenous hormones, salt, or drought
(Lee et al. 2001; Lee et al., 2012a). HOS1 does have a diurnal expression pattern showing a peak during the night in
both long- and short-day conditions (Lee et al., 2012b), but
there is no evidence that its transcription is under circadian
control (Lazaro et al., 2012). Under diurnal conditions, the
maximal amount of expression is determined by photoperiod
and is higher during long days, as confirmed with photoshift experiments (Lee et al., 2012b). Therefore, although
HOS1 is required for normal expression of nearly 9% of the
Arabidopsis genome (MacGregor et al., 2013) and environmentally responsive changes in expression of many other
genes (Ishitani et al., 1998; Lee et al., 2001; Dong et al., 2006a;
Lourenço et al., 2013; MacGregor et al., 2013), the regulation
of HOS1 itself appears to be largely post-translational rather
than at the transcript level, with the exception of the shortterm cold response.
Although it is clear that HOS1 is required for wild-type
cold signalling and cold-responsive gene expression, it is not
clear that these changes then relate back to alterations in a
plant’s ability to survive cold stress. Although overexpression
of HOS1 leads to decreased ability to survive freezing stress
(Dong et al., 2006a), electrolyte leakage tests surprisingly
show that plants with the loss-of-function allele hos1-1 or
expression of RNAi::OsHOS1 in rice also decrease freezing
tolerance in non-acclimated plants, and do not affect freezing
tolerance in acclimated plants (Ishitani et al., 1998; Lourenço
et al., 2013). These results beg the question as to whether
HOS1 has been selected through evolution as a negative regulator of cold signalling or if the role of HOS1 in this pathway
is an indirect consequence of some other function.
HOS1 negatively regulates the transition to flowering
The first report of hos1 noted its early-flowering phenotype
under long-day conditions, and suggested that hos1 mutants
displayed a constitutively vernalized phenotype (Ishitani
et al., 1998). hos1 was also independently identified in a screen
for early-flowering mutants in short-day conditions and was
called early in short days 6 (esd6) (Lazaro et al., 2012). hos1
shows early flowering under all conditions studied, including different temperature treatments such as intermittent
cold, vernalization, or growth at lower ambient temperatures
(Ishitani et al., 1998; Lee et al., 2001; Bond et al., 2011; Lee
et al., 2012a, b; Jung et al., 2012; MacGregor et al., 2013;
Jung et al., 2013). The differentially spliced isoforms appear
to have slightly different roles in the control of flowering time,
as overexpression of HOS1-L leads to later flowering than
does HOS1-S (Lee et al., 2012b), although the underlying
mechanism controlling this difference is not known.
Exploring the pleiotropy of hos1 | 1667
The flowering control pathways are an excellent example
of a highly interconnected environmental response pathway linked to developmental outputs, and FLOWERING
LOCUS C (FLC) is instrumental for control over flowering
time by temperature signalling (Michaels and Amasino, 1999;
Seo et al., 2009). FLC is a MADS-box gene that acts as a
key component in the timing control of initiation of flowering in Arabidopsis. FLC is a repressor of flowering which is
transcriptionally regulated by vernalization (Sheldon et al.,
2000; Michaels and Amasino, 1999; Henderson and Dean,
2004). The regulation of FLC by vernalization requires the
cold activation of a long antisense non-coding RNA known
as COOLAIR and the recruitment of the PRC2 complex to
silence expression through deposition of repressive chromatin marks [for reviews see Ietswaart et al. (2012) or RomeraBranchat et al. (2014)]. In hos1 the expression of FLC is
reduced, and in the control region of the FLC promoter the
epigenetic marks for active gene expression are reduced and
repressive chromatin markers increased (Lee et al., 2001;
Lazaro et al., 2012; Lee et al., 2012a; Jung et al., 2013).
Chromatin-immunoprecipitation (ChIP) using antibodies
directed against HOS1 showed enrichment of the FLC promoter, indicating that HOS1 is present at these locations
(Jung et al., 2013). Moreover, HOS1 was shown to interact
with various known chromatin regulators including FVE
and HDA6, which are known to associate in multi-protein
complexes with the regulatory region of the FLC promoter
(Pazhouhandeh et al., 2011; To et al., 2011a; Jung et al.,
2013). The level of HOS1 in planta is inversely correlated with
the enrichment of HDA6 at the promoter of FLC, and binding of HOS1 to FLC is FVE dependent but HDA6 independent (Jung et al., 2013). HOS1’s role in chromatin remodelling
is temperature dependent, as cold stress increased the enrichment of HOS1 at the FLC promoter and attenuated enrichment of HDA6 whereas FVE enrichment at the promoter of
FLC was not affected by cold treatments (Jung et al., 2013).
Therefore, in a temperature-dependent manner, HOS1 and
HDA6 compete to bind with FVE at the FLC promoter and
the combination that is present determines the state of the
chromatin and therefore the level of transcription that occurs.
The plants used for the ChIP studies were grown under constant cold or ambient temperature (Jung et al., 2013), indicating that unlike the regulation of ICE1, the role of HOS1 at
FLC is not an acute temperature response. As FLC is important for interpreting seasonal temperature cues (Michaels and
Amasino, 1999; Sheldon et al., 2000), the role of HOS1 in this
pathway means that it plays a role in processing temperature
information in response to both intermittent cold treatments
(Jung et al., 2012) as would happen during a single day and
the longer term changes that signal time of year (Jung et al.,
2013).
HOS1 affects flowering time through both FLC-dependent
and FLC-independent routes. FLC expression is reduced in
hos1 compared to the wild type under many conditions, (Lee
et al., 2001; Lazaro et al., 2012; Lee et al., 2012a; Jung et al.,
2013), although Bond et al. (2011) show that neither FLC nor
VIN3 expression is not significantly altered at ambient or low
temperatures in hos1. Double mutant analysis demonstrates
that the early-flowering phenotype of hos1 is FLC independent. For instance, although the expression of FT and its close
homologue TWIN SISTER OF FT (TSF) are increased in
hos1, this elevated expression is greater in hos1 than in flc,
and the hos1 flc double mutant shows an additive increase
in expression (Lee et al., 2012a). The hos1 flc double mutant
flowers with the same rosette leaf number as hos1, but the
double took fewer days to bolt than hos1 alone under longday conditions (Lazaro et al., 2012). Altogether, these data
indicate that there is an FLC-independent route through
which HOS1 is required for flowering-time control.
A clear mechanism for an FLC-independent role for
HOS1 in the control of flowering time under long-day conditions is through its regulation of CONSTANS (CO) protein levels through ubiquitination (Fig. 3). We know that the
HOS1-dependent ubiquitination of CO occurs through an
FLC-independent pathway because FLC expression is not
changed under conditions where CO levels increase (Jung
et al., 2012). CO is essential for the photoperiodic flowering pathway activating FLOWERING LOCUS T (FT) in
response to long days (Yanovsky and Kay, 2002; Valverde
et al., 2004). Expression of CO mRNA is under circadian
control, and CO protein is ubiquitinated by another RING
motif-containing E3 ubiquitin ligase CONSTITUTIVE
PHOTOMORPHOGENIC1 (COP1) in complex with
SUPPRESSOR OF PHYTOCHROME A-105 1 (SPA1),
which target CO for degradation specifically in the dark
(Fig. 3) (Laubinger et al., 2006; Sawa et al., 2007; Liu et al.,
2008; Jang et al., 2008). Under long-day conditions, hos1 co
double mutants flowered with the same number of leaves
as the co parent, showing that the early flowering of hos1
mutants requires CO. However, under short-day conditions,
hos1 is still early flowering, and the hos1 co double mutant
flowered as early as hos1 (Lazaro et al., 2012). Therefore, in
short days HOS1 negatively regulates flowering through a
CO-independent mechanism, whereas in long days HOS1
acts through CO to regulate flowering time.
HOS1 is required to degrade CO in the early part of the
day (Jung et al., 2012). In hos1 under both short- and longday conditions, the peak of FT expression occurred earlier
than in the wild type (Lazaro et al., 2012). HOS1 therefore
compliments the activity of COP1-SPA1, which degrades
CO during the night (Jang et al., 2008; Liu et al., 2008) to
ensure that FT expression is controlled. The synergistic activity of HOS1 and COP1 is supported by the observation that
hos1 cop1 double mutants flower earlier than the wild type or
either single mutant, and are unable to differentiate between
long- and short-day conditions (Lazaro et al., 2012). Coldinduced degradation of CO is COP1 independent as the rate
of CO degradation is greater under dark, ambient temperature conditions than it is under cold but well-lit conditions
(Jung et al., 2012). In planta, there is also a PhyB-dependent
mechanism that degrades CO early in the day (Valverde et al.,
2004; Jang et al, 2008); however, the cold-induced degradation of CO occurs independently of PhyB (Jung et al., 2012).
Because of the overlap in timing of HOS1 and PhyB degradation of CO, it has been suggested that they act through
shared processes to degrade CO (Jung et al., 2012; Lazaro
1668 | MacGregor and Penfield
et al., 2012; Endo et al., 2013), but further work is required to
demonstrate that HOS1 and PhyB work together rather than
simply at the same time of day. Altogether, these data demonstrate that HOS1 activity is required in a time- and temperature-dependent manner to maintain CO protein abundance
and prevent precocious flowering.
HOS1-mediated degradation of CO is also regulated by
temperature and there are many similarities between the regulation of CO and ICE1 by HOS1. HOS1 and CO physically
interact at their C-termini, both in vitro and in vivo (Fig. 1B)
(Jung et al., 2012; Lazaro et al., 2012). The interaction of
HOS1 and CO results in the ubiquitination of CO and its
degradation in a mechanism that requires the activity of
the 26S proteasome (Fig. 3) (Jung et al., 2012; Lazaro et al.,
2012). The level of CO ubiquitination is temperature dependent, where a reduction in temperature results in an increase in
ubiquitination (Jung et al., 2012). Finally, there is a correlation between the level and kinetics of FT expression and both
CO abundance and proteasome activity (Jung et al., 2012).
Altogether, HOS1 appears to be regulating both ICE1 and
CO in similar temperature- and ubiquitin-mediated proteasome-dependent mechanisms.
Aspects of the hos1 phenotype are also
observed in plants lacking other nuclear
pore components
hos1 mutants are not alone in showing pleiotropic growth
phenotypes. Many of the other components of the NPC have
been tested for their loss-of-function phenotypes, including
screens for phenotypes shared with hos1 as well as several
phenotypes not seen in hos1 mutants. It is, of course, possible
where mutants have not been compared beside each other,
that the phenotypes are present, but have not been observed
or recorded; therefore lack of phenotypic evidence cannot be
equated to lack of involvement in a given pathway. However,
two different reverse genetic approaches demonstrate that
members of the same sub-complexes differ in their phenotypes
when the loss-of-function mutants are compared (Wiermer
et al., 2012; Parry, 2014). These studies demonstrate that a
shared localization at the NPC or even within a protein complex does not necessarily indicate a shared syndrome. Despite
the different phenotypes that NPC mutants present, there are
some phenotypes that recur with loss of NPC function, which
suggests that these are core processes regulated by the NPC.
In Fig. 2, mutants sharing a common phenotype have been
listed in the tables at the top of the figure.
HOS1 has been characterized as a negative regulator of
cold signalling in response to cold treatment (Ishitani et al.,
1998; Lee et al., 2001; Dong et al., 2006a). RNA-sequencing
analysis of hos1 at dawn indicates that many cold-responsive
and cold-signalling genes are mis-expressed in hos1 when the
plants are kept at ambient temperatures (MacGregor et al.,
2013). The low expression of osmotically responsive genes 4
(los4/cryophyte) and suppressor of axr1 (sar1 /atnup160)
genes were identified through screens for altered cold signalling similar to that which originally identified hos1 (Gong
et al., 2005; Dong et al., 2006b). Moreover, hos1, los4, sar1/
nup160, nuclear pore anchor (nua), and the recently identified
nucleoporin mutant nup107-1 all showed a long-period circadian rhythm (MacGregor et al., 2013). Therefore correct
NPC function, circadian function, and/or cold signalling
are all commonly regulated by these genes. Although both
LOS4 and SAR1 are known to be involved in cold responses
through CBF2 or CBF3 (Gong et al., 2002; Gong et al., 2005;
Dong et al., 2006b) there is no evidence that they act through
ICE1. In fact, sar1/nup160 is known not to alter the nuclear
localization of ICE1 (Dong et al., 2006b). Likewise, neither
SAR1/NUP160 nor LOS4 have sequences that would indicate they could act as E3 ligases. As far as has been characterized, the only function that HOS1 shares with this group
of genes is their role in NPC function, specifically mRNA
export (Cernac et al., 1997; Gong et al., 2002; Gong et al.,
2005; Dong et al., 2006b; Parry et al., 2006; MacGregor et al.,
2013; Parry, 2014). mRNA export is a crucial function of
the NPC, and several NPC genes are essential for the process (Dong et al., 2006b; Parry et al., 2006; Xu et al., 2007;
Wiermer et al., 2012; MacGregor et al., 2013; Parry, 2014).
Therefore, the simplest explanation for the shared cold and
circadian phenotypes between these mutants is that wild-type
levels of mRNA export, or another aspect of RNA metabolism, is necessary for correct regulation of both processes.
As we have described above, the control of flowering time
is a complicated and highly regulated process, and as such
mutations that alter flowering time are common. Components
of each domain of the NPC, except those at the inner ring
or transmembrane ring, are required for wild-type flowering time (Ishitani et al., 1998; Lee et al., 2001; Gong et al.,
2005; Dong et al., 2006b; Parry et al., 2006; Xu et al., 2007;
Tamura et al., 2010; Bond et al., 2011; Lee et al., 2012a; Jung
et al., 2012; MacGregor et al., 2013; Jung et al., 2013; Parry,
2014). Therefore, with this many mutants all sharing altered
flowering phenotypes, it is clear that some function served by
the NPC is required for flowering-time control. Some but not
all of the mutants with flowering-time defects show altered
mRNA export, for instance nup62 has early flowering but no
alteration in mRNA export (Parry, 2014), and very few of
them have been investigated for altered cold responses or circadian period. As we compile more mechanistic detail about
the processes regulated by HOS1, it would be interesting to
apply what we have learned by studying hos1 to some of these
flowering and NPC mutants to determine which of the mechanisms are specific to HOS1 and which are specific to NPC
function.
Summary and outlook
HOS1 is the jack-of-all-trades of the NPC community. It is
a large protein with large regions of sequence that have no
identified similarity to other known domains and two alternative splice variants. HOS1 functions as a ubiquitin ligase,
binds to chromatin, and is an NPC component necessary for
mRNA export and genome-wide transcriptional control. It is
critical for repressing aberrant cold responses and the transition to flowering, and it does so by being involved in both
Exploring the pleiotropy of hos1 | 1669
day-to-day activities, like the control of circadian periodicity, as well as seasonal activities, through its ability to alter
the chromatin state of FLC. Therefore, from the molecular
level to the whole plant, and from daily to seasonal activities,
HOS1 is required for a plant to be able to sense and respond
appropriately to its environment and adapt accordingly.
HOS1 shares homology with Elys/Mel-28, which is needed
for post-mitotic reassembly of the nuclear pores, nuclear
envelope, and nuclear envelop subdomains (Galy et al.,
2006; Rasala et al., 2006; Tamura et al., 2010; Clever et al.,
2012). However, the region of homology overlaps with the
Elys region required for tethering to the NPC, not with those
needed for chromatin binding or organizational functions.
Therefore, although this homology supports the identification of HOS1 as an NPC, it does not give us the ability to
assume that they are true functional equivalents or aid in elucidating the function that HOS1 serves at the NPC. As we
accumulate information about both proteins independently,
it would be beneficial for both communities to determine how
much functional overlap there is by investigating hos1 phenotypes in loss of Elys or Mel-28 and vice versa to fully understand the roles that these proteins play, or as importantly, do
not play.
As the NPC is the gateway between cytoplasm and nucleoplasm, positioning HOS1 at the cytoplasmic or nucleoplasmic side of the complex will greatly inform conclusions made
about the role it serves. We know that HOS1 is essential for
correct mRNA export (MacGregor et al., 2013), but it is not
clear if HOS1 is required to accompany RNA from the site
of transcription through the NPC as vertebrate Nup98 is
proposed to do (Zolotukhin and Felber, 1999; Köser et al.,
2011), functions in mRNA transit through the NPC like
Nup58 (Ferrández-Ayela et al., 2013; Bonnet and Palancade,
2014), or if it functions in the exit of the mRNA from the
pore like LOS4 (Gong et al., 2005). We can speculate that
HOS1 is required at the nucleoplasmic side of the NPC
because it binds to chromatin (Jung et al., 2013), but as it
has been demonstrated to undergo temperature-dependent
nucleo-cytoplasmic partitioning (Lee et al., 2001; Lee et al.,
2012a), we cannot assume that it does not serve additional
functions away from the NPC.
HOS1 is well conserved among plants in primary amino
acid sequence, but the only function that has been tested
in other species is HOS1’s role as an E3 ligase required for
repressing cold signalling (Lourenço et al., 2013). In future
translational studies using HOS1, it would be important
to avoid analysis of one or a few of HOS1’s functions, but
instead to take a broad approach to assessing the translatability of the knowledge gained in A. thaliana to other species.
With all of the signalling pathways and molecular events that
HOS1 coordinates, it is an ideal candidate for translational
studies and real-world applications.
References
Badawi M, Reddy YV, Agharbaoui Z, Tominaga Y, Danyluk J, Sarhan
F, Houde M. 2008. Structure and functional analysis of wheat ICE (inducer
of CBF expression) genes. Plant and Cell Physiology 49, 1237–1249.
Bilokapic S, Schwartz T. 2013. Structural and functional studies of
the 252 kDa nucleoporin ELYS reveal distinct roles for its three tethered
domains. Structure 21, 572–580.
Bond D, Dennis E, Finnegan J. 2011. The low temperature response
pathways for cold acclimation and vernalization are independent. Plant,
Cell and Environment 34, 1737–1748.
Bonnet A, Palancade B. 2014. Regulation of mRNA trafficking by nuclear
pore complexes. Genes 5, 767–791.
Carré IA. 2001. Day-length perception and the photoperiodic regulation of
flowering in Arabidopsis. Journal of Biological Rhythms 16, 415–423.
Cernac A, Lincoln C, Lammer D, Estelle M. 1997. The SAR1 gene
of Arabidopsis acts downstream of the AXR1 gene in auxin response.
Development 124, 1583–1591.
Chen L, Chen Y, Jiang J, Chen S, Chen F, Guan Z, Fang W.
2012. The constitutive expression of Chrysanthemum dichrum ICE1 in
Chrysanthemum grandiflorum improves the level of low temperature,
salinity and drought tolerance. Plant Cell Reports 31, 1747–1758.
Chen Y, Jiang J, Song A, et al. 2013. Ambient temperature enhanced
freezing tolerance of Chrysanthemum dichrum CdICE1 Arabidopsis via
miR398. BMC Biology doi: 10.1186/1741-7007-11-121
Chinnusamy V, Ohta M, Kanrar S, Lee B-h, Hong X, Agarwal M, Zhu
J-K. 2003. ICE1: a regulator of cold-induced transcriptome and freezing
tolerance in Arabidopsis. Genes and Development 17, 1043–1054.
Clever M, Funakoshi T, Mimura Y, Takagi M, Imamoto N. 2012. The
nucleoporin ELYS/Mel28 regulates nuclear envelope subdomain formation
in HeLa cells. Nucleus 3, 187–199.
Denay G, Creff A, Moussu S, Wagnon P, Thévenin J, Gérentes M-F,
Chambrier P, Dubreucq B, Ingram G. 2014. Endosperm breakdown
in Arabidopsis requires heterodimers of the basic helix-loop-helix proteins
ZHOUPI and INDUCER OF CBP EXPRESSION 1. Development 141,
1222–1227.
Dong C-H, Agarwal M, Zhang Y, Xie Q, Zhu J-K. 2006a. The negative
regulator of plant cold responses, HOS1, is a RING E3 ligase that
mediates the ubiquitination and degradation of ICE1. Proceedings of the
National Academy of Sciences, USA 103, 8281–8286.
Dong C-H, Hu X, Tang W, Zheng X, Yong S, Lee B-h, Zhu J-K.
2006b. A putative Arabidopsis nucleoporin, AtNUP160, is critical for RNA
export and required for plant tolerance to cold stress. Molecular and
Cellular Biology 26, 9533–9543.
Dong C, Zhang Z, Ren J, Qin Y, Huang J, Wang Y, Cai B, Wang B,
Tao J. 2013. Stress-responsive gene ICE1 from Vitis amurensis increases
cold tolerance in tobacco. Plant Physiology and Biochemistry 71,
212–217.
Eckardt N. 2005. Temperature entrainment of the Arabidopsis circadian
clock. The Plant Cell 17, 645–647.
Endo M, Tanigawa Y, Murakami T, Araki T, Nagatani A. 2013.
PHYTOCHROME-DEPENDENT LATE-FLOWERING accelerates flowering
through physical interactions with phytochrome B and CONSTANS.
Proceedings of the National Academy of Sciences, USA 110,
18017–18022.
Feng H-L, Ma N-N, Meng X, Zhang S, Wang J-R, Chai S, Meng Q-W.
2013. A novel tomato MYC-type ICE1-like transcription factor, SlICE1a,
confers cold, osmotic and salt tolerance in transgenic tobacco. Plant
Physiology and Biochemistry 73, 309–320.
Ferrández-Ayela A, Alonso-Peral M, Sánchez-García A, MicolPonce R, Pérez-Pérez J, Micol J, Ponce M. 2013. Arabidopsis
TRANSCURVATA1 encodes NUP58, a component of the nucleopore
central channel. PLoS ONE 8, e67661.
Galy V, Askjaer P, Franz C, López-Iglesias C, Mattaj I. 2006.
MEL-28, a novel nuclear-envelope and kinetochore protein essential for
zygotic nuclear-envelope assembly in C. elegans. Current Biology 16,
1748–1756.
Gong Z, Dong C-H, Lee H, Zhu J, Xiong L, Gong D, Stevenson B,
Zhu J-K. 2005. A DEAD box RNA helicase is essential for mRNA export
and important for development and stress responses in Arabidopsis. The
Plant Cell 17, 256–267.
Gong Z, Lee H, Xiong L, Jagendorf A, Stevenson B, Zhu J-K. 2002.
RNA helicase-like protein as an early regulator of transcription factors for
plant chilling and freezing tolerance. Proceedings of the National Academy
of Sciences, USA 99, 11507–11512.
1670 | MacGregor and Penfield
Gould P, Ugarte N, Domijan M, et al. 2013. Network balance via
CRY signalling controls the Arabidopsis circadian clock over ambient
temperatures. Molecular Systems Biology 9, 650–663.
Griffis ER, Altan N, Lippincott-Schwartz J, Powers MA. 2002. Nup98
is a mobile nucleoporin with transcription-dependent dynamics. Molecular
Biology of the Cell 13, 1282–1297.
Griffis ER, Craige B, Dimaano C, Ullman K S, Powers MA. 2004.
Distinct functional domains within nucleoporins nup153 and nup98
mediate transcription-dependent mobility. Molecular Biology of the Cell 15,
1991–2002.
Henderson I, Dean C. 2004. Control of Arabidopsis flowering: the chill
before the bloom. Development 131, 3829–3838.
Hu Y, Jiang L, Wang F, Yu D. 2013. Jasmonate regulates the INDUCER
OF CBF EXPRESSION-C-REPEAT BINDING FACTOR/DRE BINDING
FACTOR1 cascade and freezing tolerance in Arabidopsis. The Plant Cell
25, 2907–2924.
Ietswaart R, Wu Z, Dean C. 2012. Flowering time control: another
window to the connection between antisense RNA and chromatin. Trends
in Genetics 28, 445–453.
Ishitani M, Xiong L, Lee H, Stevenson B, Zhu J-K. 1998. HOS1, a
genetic locus involved in cold-responsive gene expression in Arabidopsis.
The Plant Cell 10, 1151–1161.
Jang S, Marchal V, Panigrahi K, Wenkel S, Soppe W, Deng X-W,
Valverde F, Coupland G. 2008. Arabidopsis COP1 shapes the temporal
pattern of CO accumulation conferring a photoperiodic flowering response.
The EMBO Journal 27, 1277–1288.
Jin JB, Jin YH, Lee J, et al. 2008. The SUMO E3 ligase, AtSIZ1,
regulates flowering by controlling a salicylic acid-mediated floral promotion
pathway and through affects on FLC chromatin structure. The Plant
Journal 53, 530–540.
Jung J-H, Park J-H, Lee S, To TK, Kim J-M, Seki M, Park C-M. 2013.
The cold signaling attenuator HIGH EXPRESSION OF OSMOTICALLY
RESPONSIVE GENE1 activates FLOWERING LOCUS C transcription via
chromatin remodeling under short-term cold stress in Arabidopsis. The
Plant Cell 25, 4378–4390.
Jung J-H, Seo PJ, Park C-M. 2012. The E3 ubiquitin ligase HOS1
regulates Arabidopsis flowering by mediating CONSTANS degradation
under cold stress. The Journal of Biological Chemistry 287, 43277–43287.
Kanaoka M, Pillitteri L, Fujii H, Yoshida Y, Bogenschutz N,
Takabayashi J, Zhu J-K, Torii K. 2008. SCREAM/ICE1 and SCREAM2
specify three cell-state transitional steps leading to arabidopsis stomatal
differentiation. The Plant Cell 20, 1775–1785.
Keily J, MacGregor D, Smith R, Millar A, Halliday K, Penfield S.
2013. Model selection reveals control of cold signalling by evening-phased
components of the plant circadian clock. The Plant Journal 76, 247–257.
Köser J, Maco B, Aebi U, Fahrenkrog B. 2011. The nuclear pore
complex becomes alive: new insights into its dynamics and involvement
in different cellular processes. Atlas of Genetics and Cytogenetics in
Oncology and Haematology 9, 191–209.
Kurbidaeva A, Ezhova T, Novokreshchenova M. 2014. Arabidopsis
thaliana ICE2 gene: Phylogeny, structural evolution and functional
diversification from ICE1. Plant Science 229, 10–22.
Laubinger S, Marchal V, Gentilhomme J, Wenkel S, Adrian J, Jang
S, Kulajta C, Braun H, Coupland G, Hoecker U. 2006. Arabidopsis
SPA proteins regulate photoperiodic flowering and interact with the floral
inducer CONSTANS to regulate its stability. Development 133, 3213–3222.
Lazaro A, Valverde F, Piñeiro M, Jarillo J. 2012. The Arabidopsis E3
ubiquitin ligase HOS1 negatively regulates CONSTANS abundance in the
photoperiodic control of flowering. The Plant Cell 24, 982–999.
Lee B-H, Henderson D, Zhu J-K. 2005. The Arabidopsis coldresponsive transcriptome and its regulation by ICE1. The Plant Cell 17,
3155–3175.
Lee H, Xiong L, Gong Z, Ishitani M, Stevenson B, Zhu JK. 2001.
The Arabidopsis HOS1 gene negatively regulates cold signal transduction
and encodes a RING finger protein that displays cold-regulated nucleo-cytoplasmic partitioning. Genes and Development 15, 912–924.
Lee JH, Kim SH, Kim JJ, Ahn JH. 2012b. Alternative splicing and
expression analysis of High expression of osmotically responsive genes1
(HOS1) in Arabidopsis. BMB Reports 45, 515–520.
Lee J, Kim J, Kim S, Cho H, Kim J, Ahn J. 2012a. The E3 ubiquitin
ligase HOS1 regulates low ambient temperature-responsive flowering in
Arabidopsis thaliana. Plant and Cell Physiology 53, 1802–1814.
Liu L-J, Zhang Y-C, Li Q-H, Sang Y, Mao J, Lian H-L, Wang L, Yang
H-Q. 2008. COP1-mediated ubiquitination of CONSTANS is implicated
in cryptochrome regulation of flowering in arabidopsis. The Plant Cell 20,
292–306.
Lourenço T, Sapeta H, Figueiredo D, Rodrigues M, Cordeiro A,
Abreu I, Saibo N, Oliveira M. 2013. Isolation and characterization of rice
(Oryza sativa L.) E3-ubiquitin ligase OsHOS1 gene in the modulation of
cold stress response. Plant Molecular Biology 83, 351–363.
Lu Q, Tang X, Tian G, et al. 2010. Arabidopsis homolog of the yeast
TREX-2 mRNA export complex: components and anchoring nucleoporin.
The Plant Journal 61, 259–270.
MacGregor D, Gould P, Foreman J, et al. 2013. HIGH EXPRESSION
OF OSMOTICALLY RESPONSIVE GENES1 is required for circadian
periodicity through the promotion of nucleo-cytoplasmic mRNA export in
Arabidopsis. The Plant Cell 25, 4391–404.
McClung R. 2006. Plant circadian rhythms. The Plant Cell 18, 792–803.
Michaels S, Amasino R. 1999. FLOWERING LOCUS C encodes a novel
MADS domain protein that acts as a repressor of flowering. The Plant Cell
11, 949–956.
Miura K, Jin J, Lee J, Yoo C, Stirm V, Miura T, Ashworth E, Bressan
R, Yun D-J, Hasegawa P. 2007. SIZ1-mediated sumoylation of ICE1
controls CBF3/DREB1A expression and freezing tolerance in Arabidopsis.
The Plant Cell 19, 1403–1414.
Miura K, Ohta M, Nakazawa M, Ono M, Hasegawa P. 2011. ICE1
Ser403 is necessary for protein stabilization and regulation of cold
signaling and tolerance. The Plant Journal , 67, 269–279.
Parry G. 2014. Components of the Arabidopsis nuclear pore complex play
multiple diverse roles in control of plant growth. Journal of Experimental
Botany 65, 6057–6067.
Parry G, Ward S, Cernac A, Dharmasiri S, Estelle M. 2006.
The Arabidopsis SUPPRESSOR OF AUXIN RESISTANCE proteins
are nucleoporins with an important role in hormone signaling and
development. The Plant Cell 18, 1590–1603.
Pazhouhandeh M, Molinier J, Berr A, Genschik P. 2011. MSI4/FVE
interacts with CUL4–DDB1 and a PRC2-like complex to control epigenetic
regulation of flowering time in Arabidopsis. Proceedings of the National
Academy of Sciences, USA 108, 3430–3435.
Pokhilko A, Fernández AP, Edwards K, Southern M, Halliday
K, Millar A. 2012. The clock gene circuit in Arabidopsis includes a
repressilator with additional feedback loops. Molecular Systems Biology 8,
574.
Raices M, D’Angelo MA. 2012. Nuclear pore complex composition:
a new regulator of tissue-specific and developmental functions. Nature
Reviews Molecular Cell Biology 13, 687–699.
Rasala B, Orjalo A, Shen Z, Briggs S, Forbes D. 2006. ELYS is a dual
nucleoporin/kinetochore protein required for nuclear pore assembly and
proper cell division. Proceedings of the National Academy of Sciences,
USA 103, 17801–17806.
Romera-Branchat M, Andrés F, Coupland G. 2014. Flowering
responses to seasonal cues: what’s new? Current Opinion in Plant Biology
21C, 120–127.
Sawa M, Nusinow D, Kay S, Imaizumi T. 2007. FKF1 and GIGANTEA
complex formation is required for day-length measurement in Arabidopsis.
Science 318, 261–265.
Seo E, Lee H, Jeon J, Park H, Kim J, Noh Y-S, Lee I. 2009. Crosstalk
between cold response and flowering in Arabidopsis is mediated through
the flowering-time gene SOC1 and its upstream negative regulator FLC.
The Plant Cell 21, 3185–3197.
Shan W, Kuang J-F, Lu W-J, Chen J-Y. 2014. Banana fruit NAC
transcription factor MaNAC1 is a direct target of MaICE1 and involved in
cold stress through interacting with MaCBF1. Plant, Cell and Environment
37, 2116–2127.
Sheldon C, Rouse D, Finnegan J, Peacock J, Dennis E. 2000. The
molecular basis of vernalization: The central role of FLOWERING LOCUS
C (FLC). Proceedings of the National Academy of Sciences, USA 97,
3753–3758.
Exploring the pleiotropy of hos1 | 1671
Tamura K, Fukao Y, Iwamoto M, Haraguchi T, Hara-Nishimura
I. 2010. Identification and characterization of nuclear pore complex
components in Arabidopsis thaliana. The Plant Cell 22, 4084–4097.
Thomashow M. 2010. Molecular basis of plant cold acclimation: insights
gained from studying the CBF cold response pathway. Plant Physiology
154, 571–577.
To T, Kim J-M, Matsui A, et al. 2011a. Arabidopsis HDA6 regulates
locus-directed heterochromatin silencing in cooperation with MET1. PLoS
Genetics 7, e1002055.
To T, Nakaminami K, Kim J-M, Morosawa T, Ishida J, Tanaka M,
Yokoyama S, Shinozaki K, Seki M. 2011b. Arabidopsis HDA6 is
required for freezing tolerance. Biochemical and Biophysical Research
Communications 406, 414–419.
Valverde F, Mouradov A, Soppe W, Ravenscroft D, Samach A,
Coupland G. 2004. Photoreceptor regulation of CONSTANS protein in
photoperiodic flowering. Science 303, 1003–1006.
Wang Y, Jiang C-J, Li Y-Y, Wei C-L, Deng W-W. 2012. CsICE1 and
CsCBF1: two transcription factors involved in cold responses in Camellia
sinensis. Plant Cell Reports 31, 27–34.
Wiermer M, Cheng YT, Imkampe J, Li M, Wang D, Lipka V, Li X. 2012.
Putative members of the Arabidopsis Nup107-160 nuclear pore subcomplex contribute to pathogen defense. The Plant Journal 70, 796–808.
Xu W, Jiao Y, Li R, Zhang N, Xiao D, Ding X, Wang Z. 2014. Chinese
wild-growing Vitis amurensis ICE1 and ICE2 encode MYC-type bHLH
transcription activators that regulate cold tolerance in Arabidopsis. PLoS
ONE 9, e102303.
Xu X, Rose A, Muthuswamy S, Jeong S, Venkatakrishnan S, Zhao
Q, Meier I. 2007. NUCLEAR PORE ANCHOR, the Arabidopsis homolog
of Tpr/Mlp1/Mlp2/Megator, is involved in mRNA export and SUMO
homeostasis and affects diverse aspects of plant development. The Plant
Cell Online 19, 1537–1548.
Yanovsky M, Kay S. 2002. Molecular basis of seasonal time
measurement in Arabidopsis. Nature 419, 308–312.
Zhao M-L, Wang J-N, Shan W, et al. 2013. Induction of jasmonate
signalling regulators MaMYC2s and their physical interactions with MaICE1
in methyl jasmonate-induced chilling tolerance in banana fruit. Plant, Cell
and Environment 36, 30–51.
Zhu Y, Yang H, Mang H-G, Hua J. 2011. Induction of BAP1 by a
moderate decrease in temperature is mediated by ICE1 in Arabidopsis.
Plant Physiology 155, 580–588.
Zolotukhin AS, Felber BK. 1999. Nucleoporins Nup98 and Nup214
participate in nuclear export of Human Immunodeficiency Virus type 1 Rev.
Journal of Virology 73, 120–127.