title: RNA-binding protein AUF1 promotes myogenesis by regulating MEF2C expression levels.
abstract: The mammalian RNA-binding protein AUF1 (AU-binding factor 1, also known as heterogeneous nuclear ribonucleoprotein D [hnRNP D]) binds to numerous mRNAs and influences their posttranscriptional fate. Given that many AUF1 target mRNAs encode muscle-specific factors, we investigated the function of AUF1 in skeletal muscle differentiation. In mouse C2C12 myocytes, where AUF1 levels rise at the onset of myogenesis and remain elevated throughout myocyte differentiation into myotubes, RNP immunoprecipitation (RIP) analysis indicated that AUF1 binds prominently to Mef2c (myocyte enhancer factor 2c) mRNA, which encodes the key myogenic transcription factor MEF2C. By performing mRNA half-life measurements and polysome distribution analysis, we found that AUF1 associated with the 3' untranslated region (UTR) of Mef2c mRNA and promoted MEF2C translation without affecting Mef2c mRNA stability. In addition, AUF1 promoted Mef2c gene transcription via a lesser-known role of AUF1 in transcriptional regulation. Importantly, lowering AUF1 delayed myogenesis, while ectopically restoring MEF2C expression levels partially rescued the impairment of myogenesis seen after reducing AUF1 levels. We propose that MEF2C is a key effector of the myogenesis program promoted by AUF1.
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Amaresh C
authors.initials: AC
authors.lastname: Panda
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Kotb
authors.initials: K
authors.lastname: Abdelmohsen
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Je-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.affiliation: Translational Gerontology Branch, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Curtis
authors.affiliation: Translational Gerontology Branch, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Evi M
authors.initials: EM
authors.lastname: Mercken
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: Devon M
authors.initials: DM
authors.lastname: Chenette
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schneider
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.affiliation: Translational Gerontology Branch, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA myriam-gorospe@nih.gov.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics / Q000502:physiology*; D064326:MEF2 Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology*; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D012038:Regeneration / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins