title: Short intron-derived ncRNAs.
abstract: 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.
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Epigénétique et Destin Cellulaire, CNRS UMR 7216, Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Hubé
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Epigénétique et Destin Cellulaire, CNRS UMR 7216, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Ulveling
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Epigénétique et Destin Cellulaire, CNRS UMR 7216, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Sureau
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Epigénétique et Destin Cellulaire, CNRS UMR 7216, Paris, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Forveille
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Epigénétique et Destin Cellulaire, CNRS UMR 7216, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Francastel
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D019295:Computational Biology; D015894:Genome, Human; D006801:Humans; D007438:Introns / Q000235:genetics*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D012322:RNA Precursors; D022661:RNA, Untranslated