Biology Reference
In-Depth Information
fish, binds piRNAs that derive from both single-stranded transcripts
and repetitive elements.
61
4. Biogenesis of Small Regulatory RNAs
4.1. miRNA Biogenesis
Thousands of miRNAs have now been identified in various organisms,
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and the principles of biogenesis that have been inferred for lin-4 and
let-7 miRNAs generally apply to other miRNAs. Typically transcribed as
long precursors by the RNA polymerase II,
63
miRNAs form double-
stranded RNA (dsRNA) structures that are initially processed in the
nucleus by the Drosha-Pasha complex to release 50-70-nucleotide-long
pre-miRNAs.
34
These are transported through the exportin-5 system
64,65
to the cytoplasm, where the Dicer-TRBP complex releases the 21-23-
nucleotide-long dsRNA. The strand whose 5
end stability in the duplex
is minimal is then incorporated into the RISC complex,
66
whose compo-
sition has only been fully characterized in
D. melanogaster
.
66-68
Within
RISC, the miRNA acts as a guide for RNA-directed translational inhibi-
tion and mRNA degradation. The other strand, generally called
miRNA*, is degraded.
′
4.2. Biogenesis of piRNAs
piRNA biogenesis is best understood in
Drosophila
. Analysis of the
piRNAs interacting with the three members of the Piwi family of pro-
teins (Piwi, Aubergine (Aub), and Ago-3) revealed that a significant
subset of piRNAs associated with Ago-3 are derived from the sense
strand of retrotransposons, whereas the antisense strand was predomi-
nantly associated with Piwi and Aub.
17,18
The observation that many
Aub-associated small RNAs have an adenosine at position 10 led to a
model in which Ago-3 is cleaving a dsRNA precursor, generating the 5
′
end of rasiRNAs, but this model does not explain the strand selection
exhibited by the Piwi proteins. The proposed mechanism thus couples
piRNA biogenesis with their function, and implicates Piwi proteins in
the silencing of repetitive elements. The biogenesis of piRNAs in mammals
