Download Gene Section PIWIL1 (piwi like RNA mediated gene silencing 1)

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PIWIL1 (piwi-like RNA-mediated gene silencing 1)
Shozo Honda, Yohei Kirino
Department of Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical
Center, Los Angeles, California 90048, USA (SH, YK)
Published in Atlas Database: May 2013
Online updated version : http://AtlasGeneticsOncology.org/Genes/PIWIL1ID46561ch12q24.html
DOI: 10.4267/2042/51873
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2013 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Other names: HIWI, MIWI, PIWI
HGNC (Hugo): PIWIL1
Location: 12q24.33
Note: The HIWI gene belongs to an evolutionarily
conserved PIWI gene family that comprises four
members in human (PIWIL1/HIWI, PIWIL2,
PIWIL3/HILI and PIWIL4/HIWI2) (Sasaki et al.,
2003).
al., 2001). It is 3591 nt in length and comprises 21
verified exons, of which 20 are coding exons with a
total length of 2586 nt.
The 5'- and 3'-UTRs are 271 and 734 nt long,
respectively.
Variant 2 has an alternative 3'-UTR, resulting in shorter
protein with truncated C-terminus compared with
variant 1.
Variant 2 was detected by transcriptome analyses of the
"full-length long JAPAN" (FLJ) collection (Ota et al.,
2004).
DNA/RNA
Protein
Note
HIWI cDNA was first partially isolated as an ortholog
of Drosophila PIWI (Cox et al., 1998) and then fully
identified in a human testis cDNA library (Qiao et al.,
2002; Sharma et al., 2001).
Note
HIWI protein (NCBI Ref Seq: NP_004755.2) belongs
to the PIWI subgroup of Argonaute family proteins,
evolutionarily conserved proteins containing two
characteristic protein motifs, PAZ and PIWI (Carmell
et al., 2002).
Argonaute family proteins can be divided into two
subclades, AGO and PIWI, and form complexes with
small RNAs to regulate gene expressions (Carmell et
al., 2002; Hock and Meister, 2008).
Identity
Transcription
HIWI has two transcript variants. Variant 1 (NCBI Ref
Seq: NM_004764.4) was cloned from a human testis
cDNA library (Qiao et al., 2002; Sharma et
HIWI gene occupies a 34445-bp region from positions 130822433 to 130856877 on chromosome 12.
Atlas Genet Cytogenet Oncol Haematol. 2013; 17(12)
833
PIWIL1 (piwi-like RNA-mediated gene silencing 1)
Honda S, Kirino Y
2002; Houwing et al., 2008; Houwing et al., 2007;
Kuramochi-Miyagawa et al., 2004). Since 2006, the
small RNAs bound to PIWI proteins have been
identified and termed PIWI-interacting RNAs
(piRNAs) (Siomi et al., 2011).
piRNAs are 24-31 nt in length and are a highly
complex mix of sequences derived from defined
genomic regions called piRNA clusters.
Many piRNAs are derived from transposable elements,
and PIWI/piRNA complexes play a crucial role in
silencing transposons during germline development
(Siomi et al., 2011).
Description
The HIWI gene encodes an 861-amino-acid protein (98
kDa). The HIWI protein contains two characteristic
protein motifs: a PAZ domain (aa 278-413) and a PIWI
domain (aa 556-847).
In Argonaute family proteins, the PAZ domain serves
as a docking site for the 3'-end of small RNA, whereas
the PIWI domain has a structure similar to RNaseH,
which cleaves the RNA strand of an RNA-DNA hybrid
(Elkayam et al., 2012; Parker and Barford, 2006).
Indeed, all three species of the Drosophila PIWI protein
family show small RNA-guided RNA cleavage (slicer)
activity (Gunawardane et al., 2007; Nishida et al.,
2007; Saito et al., 2006).
In mouse, MIWI (mouse orthologs of HIWI) and MILI
also have the slicer activity, which is essential for
transposon silencing and fertility (De Fazio et al., 2011;
Reuter et al., 2011). In addition, the HIWI protein
contains glycine-arginine-rich repeats mainly in its Nterminus (aa 3-15:GRARARARGRARG; aa1820:GRG; aa728-730:GRG), and these are the motifs for
symmetrical dimethylarginine (sDMA) modifications
catalyzed by PRMT5 methyltransferase (Kirino et al.,
2009). sDMA positions of MIWI were determined by
mass spectrometry (Chen et al., 2009; Vagin et al.,
2009). PIWI sDMAs serve as binding elements for
TUDOR-domain containing proteins, and the sDMAdependent protein interactions play crucial roles in
piRNA function and germline development (Chen et
al., 2011; Siomi et al., 2010).
Implicated in
Various cancers
Note
Although the expression of PIWI family proteins is
normally restricted to germline cells, HIWI has been
reported to be aberrantly expressed in a variety of
cancers (Suzuki et al., 2012).
Seminoma
Note
The first report on PIWI expression in cancer was in
seminomas (Qiao et al., 2002).
HIWI was detected in seminomas but not in nonseminomas, spermatocytic seminomas, or testicular
tumors originating from somatic cells such as Sertoli
cells and Leydig cells (Qiao et al., 2002).
Gastric cancer
Expression
Note
HIWI was expressed in gastric cancer cell lines and
tissues, and its expression was correlated with
precancerous development and cell proliferation (Liu et
al., 2006).
HIWI expression was also positively correlated with T
stage, lymph node metastasis, and clinical TNM, and
patients with higher HIWI expression had shorter
survival times (Wang et al., 2012).
Expression of the PIWI protein family is restricted to
germline cells (Farazi et al., 2008).
Function
PIWI protein family was named after the Drosophila
protein PIWI (P-element induced wimpy testis)
(Carmell et al., 2002; Farazi et al, 2008).
The Drosophila PIWI was first identified in a genetic
screen for mutants that affect stem cell division in the
germline, and subsequent studies demonstrated that
Drosophila PIWI is essential for gametogenesis and is a
key regulator of female germline stem cells (Cox et al.,
1998; Cox et al., 2000; Lin and Spradling, 1997).
PIWI protein mutations in various organisms, including
mice and zebrafish, commonly cause defects in
gametogenesis, indicating evolutionarily conserved
essential roles for PIWI proteins in germline
development (Carmell et al., 2007; Deng and Lin,
Atlas Genet Cytogenet Oncol Haematol. 2013; 17(12)
Sarcoma
Note
An increased expression of HIWI mRNA was
correlated with prognosis of patients with soft-tissue
sarcomas (Taubert et al., 2007).
HIWI expression promoted sarcomagenesis in cells,
developed sarcoma in mice, and correlated with DNA
methylation in sarcoma cells (Siddiqi et al., 2012).
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PIWIL1 (piwi-like RNA-mediated gene silencing 1)
Honda S, Kirino Y
Pancreatic cancer
References
Note
Patients with altered levels of HIWI mRNA had
increased risk of tumor-related death (Grochola et al.,
2008).
Lin H, Spradling AC. A novel group of pumilio mutations affects
the asymmetric division of germline stem cells in the
Drosophila ovary. Development. 1997 Jun;124(12):2463-76
Cox DN, Chao A, Baker J, Chang L, Qiao D, Lin H. A novel
class of evolutionarily conserved genes defined by piwi are
essential for stem cell self-renewal. Genes Dev. 1998 Dec
1;12(23):3715-27
Esophageal cancer
Note
The cytoplasmic expression of HIWI significantly
correlated with histological grade and poorer clinical
outcome (He et al., 2009).
Cox DN, Chao A, Lin H. piwi encodes a nucleoplasmic factor
whose activity modulates the number and division rate of
germline stem cells. Development. 2000 Feb;127(3):503-14
Sharma AK, Nelson MC, Brandt JE, Wessman M, Mahmud N,
Weller KP, Hoffman R. Human CD34(+) stem cells express the
hiwi gene, a human homologue of the Drosophila gene piwi.
Blood. 2001 Jan 15;97(2):426-34
Cervical cancer
Note
Elevated HIWI expression was associated with cervical
cancer invasion and human papillomavirus infection,
but not with patient age or histological grade (Liu et al.,
2010a).
Carmell MA, Xuan Z, Zhang MQ, Hannon GJ. The Argonaute
family: tentacles that reach into RNAi, developmental control,
stem cell maintenance, and tumorigenesis. Genes Dev. 2002
Nov 1;16(21):2733-42
Endometrial cancer
Deng W, Lin H. miwi, a murine homolog of piwi, encodes a
cytoplasmic protein essential for spermatogenesis. Dev Cell.
2002 Jun;2(6):819-30
Note
HIWI was expressed in endometrial adenocarcinoma
but did not correlate with pathological features (Liu et
al., 2010b).
Qiao D, Zeeman AM, Deng W, Looijenga LH, Lin H. Molecular
characterization of hiwi, a human member of the piwi gene
family whose overexpression is correlated to seminomas.
Oncogene. 2002 Jun 6;21(25):3988-99
Glioma
Sasaki T, Shiohama A, Minoshima S, Shimizu N. Identification
of eight members of the Argonaute family in the human
genome small star, filled. Genomics. 2003 Sep;82(3):323-30
Note
The expression level of HIWI was positively correlated
with tumor grade, and patients with high HIWI
expression had poorer clinical outcomes (Sun et al.,
2011).
Kuramochi-Miyagawa S, Kimura T et al.. Mili, a mammalian
member of piwi family gene, is essential for spermatogenesis.
Development. 2004 Feb;131(4):839-49
Colon cancer
Ota T, Suzuki Y, Nishikawa T, Otsuki T et al.. Complete
sequencing and characterization of 21,243 full-length human
cDNAs. Nat Genet. 2004 Jan;36(1):40-5
Note
In colorectal cancer, HIWI expression in early stage
and in adjacent non-cancerous tissues negatively
correlated with survival rates and times of the patients
(Zeng et al., 2011).
Among colon cancer patients without lymph node
metastasis, those with HIWI-positive tumors had a
significantly lower survival rate than those with HIWInegative tumors (Liu et al., 2012).
Liu X, Sun Y, Guo J, Ma H, Li J, Dong B, Jin G, Zhang J, Wu J,
Meng L, Shou C. Expression of hiwi gene in human gastric
cancer was associated with proliferation of cancer cells. Int J
Cancer. 2006 Apr 15;118(8):1922-9
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short regulatory RNAs. Trends Biochem Sci. 2006
Nov;31(11):622-30
Saito K, Nishida KM, Mori T, Kawamura Y, Miyoshi K, Nagami
T, Siomi H, Siomi MC. Specific association of Piwi with
rasiRNAs derived from retrotransposon and heterochromatic
regions in the Drosophila genome. Genes Dev. 2006 Aug
15;20(16):2214-22
Liver cancer
Note
HIWI expression in hepatocellular carcinoma tissues
was significantly higher than in adjacent normal
hepatic tissue and was correlated with metastasis (Jiang
et al., 2011). HIWI expression positively correlated
with tumor size and metastasis and negatively
correlated with survival rates in hepatocellular
carcinoma cells and tissues (Zhao et al., 2012).
Carmell MA, Girard A, van de Kant HJ, Bourc'his D, Bestor TH,
de Rooij DG, Hannon GJ. MIWI2 is essential for
spermatogenesis and repression of transposons in the mouse
male germline. Dev Cell. 2007 Apr;12(4):503-14
Gunawardane LS, Saito K, Nishida KM, Miyoshi K, Kawamura
Y, Nagami T, Siomi H, Siomi MC. A slicer-mediated
mechanism for repeat-associated siRNA 5' end formation in
Drosophila. Science. 2007 Mar 16;315(5818):1587-90
Lung cancer
Houwing S, Kamminga LM, Berezikov E et al.. A role for Piwi
and piRNAs in germ cell maintenance and transposon
silencing in Zebrafish. Cell. 2007 Apr 6;129(1):69-82
Note
HIWI knockdown decreased cell proliferation and
promoted apoptosis of lung cancer stem cells (Liang et
al., 2013; Liang et al., 2012).
Atlas Genet Cytogenet Oncol Haematol. 2013; 17(12)
Nishida KM, Saito K, Mori T, Kawamura Y, Nagami-Okada T,
Inagaki S, Siomi H, Siomi MC. Gene silencing mechanisms
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PIWIL1 (piwi-like RNA-mediated gene silencing 1)
Honda S, Kirino Y
mediated by Aubergine piRNA complexes in Drosophila male
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tumour-related death in patients with soft-tissue sarcoma.
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This article should be referenced as such:
Atlas Genet Cytogenet Oncol Haematol. 2013; 17(12)
Honda S, Kirino Y. PIWIL1 (piwi-like RNA-mediated gene
silencing 1). Atlas Genet Cytogenet Oncol Haematol. 2013;
17(12):833-836.
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