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1. Genome-wide exploration of miRNA function in mammalian muscle cell differentiation.

Author

Anna Polesskaya, Cindy Degerny, Guillaume Pinna, Yves Maury, Gueorgui Kratassiouk, Vincent Mouly, Nadya Morozova, Jeremie Kropp, Niels Frandsen, and Annick Harel-Bellan

Subjects
Medicine, Science
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.

Published
2013
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2. Genome-Wide Exploration of miRNA Function in Mammalian Muscle Cell Differentiation

Author

Annick Harel-Bellan, Jeremie Kropp, Vincent Mouly, Cindy Degerny, Niels Erik Frandsen, Gueorgui Kratassiouk, Guillaume Pinna, Yves Maury, Anna Polesskaya, and Nadya Morozova

Subjects
Anatomy and Physiology, Science, Cellular differentiation, Myoblasts, Skeletal, Blotting, Western, Muscle Proteins, Biology, Cell fate determination, Cell Line, Myoblasts, RNA interference, microRNA, Molecular Cell Biology, Genetics, Gene silencing, Animals, Humans, Musculoskeletal System, Oligonucleotide Array Sequence Analysis, Regulation of gene expression, Gene knockdown, Muscle Cells, Multidisciplinary, Genome, Human, Reverse Transcriptase Polymerase Chain Reaction, Systems Biology, Gene Expression Profiling, Gene Expression Regulation, Developmental, Cell Differentiation, Genomics, Cell biology, Functional Genomics, Gene expression profiling, MicroRNAs, Gene Knockdown Techniques, Medicine, Muscle, Gene expression, Cellular Types, Genetic screen, Research Article, Developmental Biology
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.

Published
2013

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