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have become extremely important non-conventional drug targets
for therapeutic intervention [
4
,
5
,
26
-
29
].
The biogenesis of miRNAs involves nuclear transcription by
RNA polymerase II of endogenously encoded primary miRNAs
(pri-miRNAs) 100-1,000 nucleotides in length (Fig.
1
) [
10
,
30
].
Pri-miRNAs are then further processed in the nucleus into stem-loop-
structured precursor-miRNAs (pre-miRNAs) of 60-80 nucleotides
in length, which are exported into the cytoplasm [
31
,
32
]. At this
stage pre-miRNAs behave in an analogous fashion to exogenously
introduced double-stranded RNAs used to produce siRNAs as pre-
miRNAs are further digested to 21-23 nucleotide mature miRNAs
by the enzyme Dicer (in conjunction with partnering proteins) and
are loaded into the RNA-induced silencing complex (RISC) [
33
,
34
].
At this stage the RNA is unwound and the active miRNA strand is
used to site-specifi cally repress mRNA translation. While the exact
mechanism of translational repression has yet to be fully elucidated
Fig. 1
The representative miRNA maturation pathway leading to gene silencing. Image adapted with permis-
sion from Winter J et al. (2009) Nat Cell Biol
