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2018 ; 19
(Suppl 3
): 114
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Comparing miRNA structure of mirtrons and non-mirtrons
#MMPMID29504892
Titov II
; Vorozheykin PS
BMC Genomics
2018[Feb]; 19
(Suppl 3
): 114
PMID29504892
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BACKGROUND: MicroRNAs proceeds through the different canonical and non-canonical
pathways; the most frequent of the non-canonical ones is the splicing-dependent
biogenesis of mirtrons. We compare the mirtrons and non-mirtrons of human and
mouse to explore how their maturation appears in the precursor structure around
the miRNA. RESULTS: We found the coherence of the overhang lengths what indicates
the dependence between the cleavage sites. To explain this dependence we suggest
the 2-lever model of the Dicer structure that couples the imprecisions in Drosha
and Dicer. Considering the secondary structure of all animal pre-miRNAs we
confirmed that single-stranded nucleotides tend to be located near the miRNA
boundaries and in its center and are characterized by a higher mutation rate. The
5' end of the canonical 5' miRNA approaches the nearest single-stranded
nucleotides what suggests the extension of the loop-counting rule from the Dicer
to the Drosha cleavage site. A typical structure of the annotated mirtron
pre-miRNAs differs from the canonical pre-miRNA structure and possesses the 1-
and 2 nt hanging ends at the hairpin base. Together with the excessive
variability of the mirtron Dicer cleavage site (that could be partially explained
by guanine at its ends inherited from splicing) this is one more evidence for the
2-lever model. In contrast with the canonical miRNAs the mirtrons have higher snp
densities and their pre-miRNAs are inversely associated with diseases. Therefore
we supported the view that mirtrons are under positive selection while canonical
miRNAs are under negative one and we suggested that mirtrons are an intrinsic
source of silencing variability which produces the disease-promoting variants.
Finally, we considered the interference of the pre-miRNA structure and the
U2snRNA:pre-mRNA basepairing. We analyzed the location of the branchpoints and
found that mirtron structure tends to expose the branchpoint site what suggests
that the mirtrons can readily evolve from occasional hairpins in the immediate
neighbourhood of the 3' splice site. CONCLUSION: The miRNA biogenesis manifests
itself in the footprints of the secondary structure. Close inspection of these
structural properties can help to uncover new pathways of miRNA biogenesis and to
refine the known miRNA data, in particular, new non-canonical miRNAs may be
predicted or the known miRNAs can be re-classified.
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