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2017 ; 45
(8
): 4768-4781
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Short intron-derived ncRNAs
#MMPMID28053119
Hubé F
; Ulveling D
; Sureau A
; Forveille S
; Francastel C
Nucleic Acids Res
2017[May]; 45
(8
): 4768-4781
PMID28053119
show ga
Introns represent almost half of the human genome, although they are eliminated
from transcripts through RNA splicing. Yet, different classes of non-canonical
miRNAs have been proposed to originate directly from intron splicing. Here, we
considered the alternative splicing of introns as an interesting source of
miRNAs, compatible with a developmental switch. We report computational
prediction of new Short Intron-Derived ncRNAs (SID), defined as precursors of
smaller ncRNAs like miRNAs and snoRNAs produced directly by splicing, and tested
their dependence on each key factor in canonical or alternative miRNAs biogenesis
(Drosha, DGCR8, DBR1, snRNP70, U2AF65, PRP8, Dicer, Ago2). We found that about
half of predicted SID rely on debranching of the excised intron-lariat by the
enzyme DBR1, as proposed for mirtrons. However, we identified new classes of SID
for which miRNAs biogenesis may rely on intermingling between canonical and
alternative pathways. We validated selected SID as putative miRNAs precursors and
identified new endogenous miRNAs produced by non-canonical pathways, including
one hosted in the first intron of SRA (Steroid Receptor RNA activator).
Consistent with increased SRA intron retention during myogenic differentiation,
release of SRA intron and its associated mature miRNA decreased in cells from
healthy subjects but not from myotonic dystrophy patients with splicing defects.
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