ncRNAs
What Genomes are Telling Us
ncrna.ppt
ncRNA genes are difficult to discover!
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small
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no ORFs and no polyadenylation
must be identified by paralogy/orthology
novel members not readily discovered from sequence
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Draft or complete; no structural information; underrepresentation
draft sequence biased against tandem ncRNA gene units
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an annotational and statistical concern
“low complexity” BACs not sequenced for draft
many pseudogenes and retropseudogenes
difficult to distinguish gene from pseudogene
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except tRNA genes
The ncRNAs We Know and Love
•snRNAs
•snoRNAs
•rRNAs
•Telomerase RNA
•tRNAs
•Xist RNA
•Snurp RNAs
•Vault RNA
•7SL RNA
•miRNAs
Transfer RNAs (tRNAs)
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About 500 genes, about 300 pseudogenes
Included tRNASeCys-UGA
Fly < Humans < Worm
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Related to developmental and tissue-specific needs, not
organismal complexity
tRNAaa gene number roughly correlates with
aa frequency and codon bias
Genomic distribution of tRNA genes
in human
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Nonrandom dispersal (clustering)
25% (140) located in 4 Mb of HSA6
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0.1% of genome has near complete set of anticodons
18 of 30 tRNAcys genes located in 0.5MB of HSA7
Many tRNAarg and tRNAglu are loosely clustered on
HSA1
Over 50% (280) genes located on HSA1&6
HSA3,4,8,9,10,12,18,20,21 and X have <10 tRNA
genes each
HSA22 and Y have one pseudogene each and no
genes
Ribosomal RNAs (rRNAs)
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Four RNA molecules for each of two ribosome
subunits
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LSU and SSU rRNA genes occur as 44kb tandem
repeat unit
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LSU rRNA = 28S, 5.8S
SSU rRNA = 18S
5S rRNA (also part of LSU but from separate gene)
150-200 copies on the short arms of acrocentric chromosomes 13,
14, 15, 21, 22
5S rRNA gene occurs in several 200-300-unit tandem
arrays
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Largest at 1q41.11-1q42.13
2000 copies predicted; 520 pseudogenes likely
LSU-SSU rRNA
gene repeat:
150-200 copies on
HSA 13p, 14p, 15p,
21p, 22p
Small nucleolar RNAs (snoRNAs)
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direct postranscriptional modification and processing
of rRNAs in nucleolus
Two families of snoRNA genes
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97 snoRNA genes
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C/D-Box snoRNAs direct 2’-O-ribose methylations (105-107
instances)
H/ACA-Box snoRNAs direct pseudouridylation (95 instances)
Distributed across chromosomes as nearly all single copies
5-10 copies of CD-Box snoRNA gene inverted repeats at 17q21
More predicted
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Sequences diverse; cannot depend on paralogy to predict
Spliceosomal snRNAs (snurps)
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Ten known RNAs (U1-U12) responsible for hnRNA
splicing
Snurp RNAs either clustered or dispersed:
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44 dispersed genes for U6 RNA
16 dispersed genes for U1 RNA
10-20 tandem copies U2 RNA genes (6.1 kb units) at 17q21
30 copy loose cluster of U1 RNA genes at 1p36
More predicted
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Tandem-arrayed clusters underrepresented in draft
ncRNA pseuodgenes
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100’s-1000’s of pseudogene copies of ncRNA genes
More copies from ncRNAs transcribed by RNA
polymerase III
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Most presumed to have arisen by reverse
transcription and retroposition
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Including snurp U6, 7 SL RNA, and hY RNA
Like Alu and tRNA-family repeats
Analytical comparison with Alus may help explain
requirements for SINE proliferation in genomes
Dude!
Small interfering RNAs (siRNAs)
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siRNA-containing transcripts exhibit extensive
folding
dsRNA folds recognized by DICER enzyme
siRNA molecules excised from folds in nucleus or
cytoplasm
snRNA perform multiple functions
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Directed degredation of specific mRNAs
Maintenance of heterochromatin
Analogous to RNAi experiments, but siRNA is
endogenous
RISC
RNA
induced
silencing
complex
microRNAs (miRNAs)
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~21 nts long
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miRNAs derive from 60-80 nt dsRNA hairpins
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Hairpins excised from primaries in nucleus
Some transcripts have exon-intron structure
 miRNAs can derive from instron or exon sequence
Some transcripts contain clusters of miRNAs
Conserved sequence
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miRNAs excised from hairpins in cytoplasm
Excised by DICER
Hairpins derive from long primary transcripts
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“mature” miRNA
50% have Fugu and Danio homologues
25% have C. elegans homologues
Primary function believed to be translational suppression
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Binds to target mRNAs at 3’ ends
Suppresses, slows, or eliminates specific protein synthesis
Some act as siRNAs
A Few Parting Words on cRNAs and their Genes