Biology Reference
In-Depth Information
counterpart the miRNA* passenger strand, it has been shown that
the RNA strand which is less thermodynamically stable at the 5
end
is designated as the miRNA guide strand whereas the remaining
strand will become the miRNA* passenger strand which is usually
discarded [
11
,
47
,
48
]. Nevertheless miRNA* strands show regu-
latory function in vertebrates and have Ago sorting characteristics
in Drosophila [
49
-
55
]. Once bound, dsRNAs undergo signifi cant
repositioning within the Dicer complex following dicing which
enables directional binding of RNA duplexes. There are two dis-
tinct RNA-binding sites within the Dicer complex—one for dsRNA
processing and the other for sensing thermodynamic asymmetry
which facilitates guide strand selection during RISC loading in
humans [
56
]. Once the mature miRNA guide strand has been
loaded on the RISC, the miRNA/RISC complex is ready to anneal
to the target mRNA in the so-called miRNA seed region on nts
2-7. In the event of nearly complete complementarity the target
mRNA is cleaved endonucleolytically resulting in a cessation of
translation, while translation is only suppressed in case of limited
complementarity [
57
,
58
].
′
4
Mirtrons: The First Alternative miRNA Maturation Pathway
After the canonical miRNA pathway had been specifi ed as previ-
ously illustrated a growing number of noncanonical miRNA path-
ways have been described [
55
,
59
]. The fi rst and most important
alternative miRNA maturation pathway described is the “mirtron”
pathway.
Mirtrons are directly spliced out from host genes as pre-
miRNAs with hairpin potential and do not depend on pri-miRNA
Drosha/DGCR8 processing. The product of intron splicing is not
linear but mimics a transient lariat shape wherein the 3
′
branch-
point is ligated to the 5
end of the intron. After the lariat-shape
intron is processed by the lariat debranching enzyme (Ldbr) it
refolds into a pre-miRNA shape which is recognized and trans-
ferred to the cytoplasm by Exp-5. Following regular Dicer cleavage
the mature miRNA can be loaded on the RISC and exerts its effect.
′
References
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