Novel Long Noncoding RNAs (lncRNAs) in Myogenesis: a miR-31 Overlapping lncRNA Transcript Controls Myoblast Differentiation

Abstract

Transcriptome analysis allowed the identification of new long noncoding RNAs differentially expressed during murine myoblast differentiation. These transcripts were classified on the basis of their expression under proliferating versus differentiated conditions, muscle-restricted activation, and subcellular localization. Several species displayed preferential expression in dystrophic (mdx) versus wild-type muscles, indicating their possible link with regenerative processes. One of the identified transcripts, lnc-31, even if originating from the same nuclear precursor of miR-31, is produced by a pathway mutually exclusive. We show that lnc-31 and its human homologue hsa-lnc-31 are expressed in proliferating myoblasts, where they counteract differentiation. In line with this, both species are more abundant in mdx muscles and in human Duchenne muscular dystrophy (DMD) myoblasts, than in their normal counterparts. Altogether, these data suggest a crucial role for lnc-31 in controlling the differentiation commitment of precursor myoblasts and indicate that its function is maintained in evolution despite the poor sequence conservation with the human counterpart.

Long noncoding RNAs and their roles in skeletal muscle fate determination

“…Sirt1 antisense lncRNA (AS lncRNA), through interaction with miR-34a, negatively regulates myoblast proliferation and differentiation (24). Lastly, lnc-31 acts to inhibit differentiation and maintain proliferation (25). …”

Noncoding RNAs in the regulation of skeletal muscle biology in health and disease

“…For example, linc-MD1, Metastasis-associated lung adenocarcinoma transcript 1 (Malat1), Core enhancer RNA ( CE RNA), Distal regulatory regions RNA ( DRR RNA), MUNC, lncMyoD, and Steroid Receptor RNA activator (SRA) lncRNAs promote myogenesis, whereas Mouse Staufen1-binding site RNAs (m½-sbsRNAs) inhibit myogenesis, or both (H19) [27, 57-65, 76]. Furthermore, levels of a few lncRNAs such as lnc-31 and YY1-associated muscle lincRNA (Yam-1), which inhibit myogenic differentiation, are repressed after incubation of myoblasts in low serum conditions [59, 66]. …”

“…In contrast to linc-MD1, lnc-31 may inhibit myogenic differentiation, although the mechanism remains unknown [59]. Interestingly, lnc-31 controls muscle differentiation independently from miR-31, in spite of genomic overlapping with the miR-31 coding region [59].…”

“…Interestingly, lnc-31 controls muscle differentiation independently from miR-31, in spite of genomic overlapping with the miR-31 coding region [59]. Finally, m½-sbsRNAs are largely cytoplasmic and polyadenylated lncRNAs which belong to the class of Short-interspersed element (SINE)-containing lncRNAs.…”

“…Although the role of these lncRNAs in the pathogenesis of DMD remains unknown, some of them repress the expression of endogenous full-length dystrophin isoforms through interactions with the dystrophin promoter [98]. The lncRNA lnc-31, which promotes myoblast proliferation but inhibits differentiation, is upregulated in skeletal muscles of mdx mice and in skeletal muscles of DMD patients [59]. However, the potential role of lnc-31 in the pathophysiology of DMD has not yet been investigated.…”