Abstract:
:A number of microRNAs have been shown to regulate skeletal muscle development and differentiation. MicroRNA-222 is downregulated during myogenic differentiation and its overexpression leads to alteration of muscle differentiation process and specialized structures. By using RNA-induced silencing complex (RISC) pulldown followed by RNA sequencing, combined with in silico microRNA target prediction, we have identified two new targets of microRNA-222 involved in the regulation of myogenic differentiation, Ahnak and Rbm24. Specifically, the RNA-binding protein Rbm24 is a major regulator of muscle-specific alternative splicing and its downregulation by microRNA-222 results in defective exon inclusion impairing the production of muscle-specific isoforms of Coro6, Fxr1 and NACA transcripts. Reconstitution of normal levels of Rbm24 in cells overexpressing microRNA-222 rescues muscle-specific splicing. In conclusion, we have identified a new function of microRNA-222 leading to alteration of myogenic differentiation at the level of alternative splicing, and we provide evidence that this effect is mediated by Rbm24 protein.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Cardinali B,Cappella M,Provenzano C,Garcia-Manteiga JM,Lazarevic D,Cittaro D,Martelli F,Falcone Gdoi
10.1038/cddis.2016.10subject
Has Abstractpub_date
2016-02-04 00:00:00pages
e2086issn
2041-4889pii
cddis201610journal_volume
7pub_type
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