title: MicroRNA-222 regulates muscle alternative splicing through Rbm24 during differentiation of skeletal muscle cells.
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.
authors: Institute of Cell Biology and Neurobiology, National Research Council, Monterotondo Scalo, Rome, Italy.
authors: B
authors: B
authors: Cardinali
authors: Institute of Cell Biology and Neurobiology, National Research Council, Monterotondo Scalo, Rome, Italy.|DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.
authors: M
authors: M
authors: Cappella
authors: Institute of Cell Biology and Neurobiology, National Research Council, Monterotondo Scalo, Rome, Italy.
authors: C
authors: C
authors: Provenzano
authors: Center For Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy.
authors: J M
authors: JM
authors: Garcia-Manteiga
authors: Center For Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy.
authors: D
authors: D
authors: Lazarevic
authors: Center For Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy.
authors: D
authors: http://orcid.org/0000-0003-0384-3700
authors: D
authors: Cittaro
authors: Molecular Cardiology Laboratory, Policlinico San Donato-IRCCS, San Donato Milanese, Milan, Italy.
authors: F
authors: F
authors: Martelli
authors: Institute of Cell Biology and Neurobiology, National Research Council, Monterotondo Scalo, Rome, Italy.
authors: G
authors: G
authors: Falcone
mesh_terms: D017398:Alternative Splicing; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016601:RNA-Binding Proteins; C525710:MIR222, human; C000594453:RBM24 protein, human