Download Small Nucleolar RNA

Small Nucleolar RNA
Megan Salt
BMS 265 – Macromolecules
Special Topics in Nucleic Acids
Discovery of snoRNAs
U3 snoRNA
Wikipedia
• First snoRNA found in
late 1960’s (U3)
• Band representing sn and
snoRNAs seen from rat
nuclei
• High uridine content led
to naming convention
There are several mechanisms of snoRNA
biosynthesis
• Yeast snoRNAs are
generally monocistronic
• Plants generate
polycistronic snoRNAs
• Vertebrate snoRNAs are
often within introns of
rRNA processing genes
Monocistronic
Polycistronic
Intronic
There are several mechanisms of snoRNA
biosynthesis
• Polycistronic and intronic snoRNAs require further
processing to function
Endonucleases
5’
3’
Exonucleases
Splicing machinery
snoRNAs mediate the modification of other
RNA nucleotides
2’-O-methylation
• Human 18S, 5.8S, and 28S
rRNAs contain 110 2'-Omethyl groups and almost
100 pseudouridines
• snoRNAs direct
methyltransferase and
pseudouridine synthase
enzymes to the appropriate
rRNA nucleotide
Pseudouridylation
snoRNAs act to guide nucleotide modifying
enzymes to the proper rRNA site
• Antisense elements dictate where the
modifications are catalyzed
Filipowicz et al. 2002
• Target sequences have been confirmed also in
snRNAs, as well as mRNAs
snoRNAs function as part of a
ribonucleoprotein complex
Filipowicz et al. 2002
Evolution of snoRNAs
Lafontaine et al. 1998.
• Enzymes likely evolved from gene duplications
of tRNA or rRNA processing enzymes
• Ancestral snoRNAs likely guided these
enzymes and acquired specificities for novel
rRNA sites
snoRNAs can be used as a biological tool
• (1) snoRNA localization elements have been
utilized to direct new RNA sequences to the
nucleolus
• (2) snoRNAs have been used to direct
nucleotide modifications to new sites in rRNA
via the expression of snoRNAs containing
novel guide sequences
snoRNAs have been implicated in human
disease
• HBII-52 snoRNA involved in modification of
serotonin receptor mRNA
• Loss of either the paternal or maternal copy of
this region leads to two neurological
disorders: Prader-Willi or Angelman
syndrome, respectively
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