title: Genome-wide exploration of miRNA function in mammalian muscle cell differentiation.
abstract: MiRNAs impact on the control of cell fate by regulating gene expression at the post-transcriptional level. Here, using mammalian muscle differentiation as a model and a phenotypic loss-of-function screen, we explored the function of miRNAs at the genome-wide level. We found that the depletion of a high number of miRNAs (63) impacted on differentiation of human muscle precursors, underscoring the importance of this post-transcriptional mechanism of gene regulation. Interestingly, a comparison with miRNA expression profiles revealed that most of the hit miRNAs did not show any significant variations of expression during differentiation. These constitutively expressed miRNAs might be required for basic and/or essential cell function, or else might be regulated at the post-transcriptional level. MiRNA inhibition yielded a variety of phenotypes, reflecting the widespread miRNA involvement in differentiation. Using a functional screen (the STarS--Suppressor Target Screen--approach, i. e. concomitant knockdown of miRNAs and of candidate target proteins), we discovered miRNA protein targets that are previously uncharacterized controllers of muscle-cell terminal differentiation. Our results provide a strategy for functional annotation of the human miRnome.
authors.affiliation: Department Epigenetics and Cancer FRE 3377, Centre National de la Recherche Scientifique, Commissariat à l'Energie Atomique Saclay, Gif-sur-Yvette, France ; Université Paris-Sud, Gif-sur-Yvette, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Polesskaya
authors.forename: Cindy
authors.initials: C
authors.lastname: Degerny
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pinna
authors.forename: Yves
authors.initials: Y
authors.lastname: Maury
authors.forename: Gueorgui
authors.initials: G
authors.lastname: Kratassiouk
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.forename: Nadya
authors.initials: N
authors.lastname: Morozova
authors.forename: Jeremie
authors.initials: J
authors.lastname: Kropp
authors.forename: Niels
authors.initials: N
authors.lastname: Frandsen
authors.forename: Annick
authors.initials: A
authors.lastname: Harel-Bellan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D009124:Muscle Proteins