MicroRNA-222 regulates muscle alternative splicing through Rbm24 during differentiation of skeletal muscle cells

B. Cardinali, M. Cappella, C. Provenzano, Jose Manuel Garcia Manteiga, D. Lazarevic, D. Cittaro, F. Martelli, G. Falcone

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Article numbere2086
JournalCell Death and Disease
Volume7
DOIs
Publication statusPublished - Feb 4 2016

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Alternative Splicing
MicroRNAs
Muscle Cells
Skeletal Muscle
Muscles
Down-Regulation
RNA-Induced Silencing Complex
RNA Sequence Analysis
RNA-Binding Proteins
Muscle Development
Computer Simulation
Exons
Protein Isoforms
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience

Cite this

MicroRNA-222 regulates muscle alternative splicing through Rbm24 during differentiation of skeletal muscle cells. / Cardinali, B.; Cappella, M.; Provenzano, C.; Garcia Manteiga, Jose Manuel; Lazarevic, D.; Cittaro, D.; Martelli, F.; Falcone, G.

In: Cell Death and Disease, Vol. 7, e2086, 04.02.2016.

Research output: Contribution to journalArticle

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AU - Garcia Manteiga, Jose Manuel

AU - Lazarevic, D.

AU - Cittaro, D.

AU - Martelli, F.

AU - Falcone, G.

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AB - 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.

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