1. RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes
- Author
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Stacey R. Gundry, Leonard I. Zon, Marie-Françoise O'Donohue, Anirban Chakraborty, Alexis H Bennett, Jeffrey J. Widrick, Yi Zhou, Alan H. Beggs, Vandana Gupta, Pierre-Emmanuel Gleizes, Isabelle Draper, Aye T. Chan, University of Electronic Science and Technology of China (UESTC), Harvard University [Cambridge], Laboratoire de biologie moléculaire eucaryote (LBME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Boston Children's Hospital
- Subjects
0301 basic medicine ,Cancer Research ,Embryo, Nonmammalian ,[SDV]Life Sciences [q-bio] ,Immunofluorescence ,Ribosome biogenesis ,Muscle Development ,Ribosome ,Biochemistry ,Myoblasts ,Animals, Genetically Modified ,DEAD-box RNA Helicases ,Mice ,0302 clinical medicine ,Animal Cells ,Gene expression ,Translational regulation ,Protein biosynthesis ,Medicine and Health Sciences ,Morphogenesis ,Musculoskeletal System ,Genetics (clinical) ,ComputingMilieux_MISCELLANEOUS ,Zebrafish ,0303 health sciences ,Myogenesis ,Muscles ,Stem Cells ,Eukaryota ,Translation (biology) ,Animal Models ,Non-coding RNA ,Muscle Differentiation ,RNA Helicase A ,3. Good health ,Cell biology ,Nucleic acids ,Experimental Organism Systems ,Ribosomal RNA ,Osteichthyes ,Vertebrates ,Anatomy ,Cellular Types ,Muscle Regeneration ,Cell Nucleolus ,Research Article ,Cellular structures and organelles ,lcsh:QH426-470 ,Biology ,Research and Analysis Methods ,Cell Line ,03 medical and health sciences ,Model Organisms ,Genetics ,Animals ,Regeneration ,Immunoassays ,Muscle, Skeletal ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,Cell Proliferation ,PAX2 Transcription Factor ,Organisms ,Biology and Life Sciences ,Zebrafish Proteins ,lcsh:Genetics ,030104 developmental biology ,Fish ,Skeletal Muscles ,RNA, Ribosomal ,Protein Biosynthesis ,Immunologic Techniques ,RNA ,Ribosomes ,Organism Development ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Gene expression in a tissue-specific context depends on the combined efforts of epigenetic, transcriptional and post-transcriptional processes that lead to the production of specific proteins that are important determinants of cellular identity. Ribosomes are a central component of the protein biosynthesis machinery in cells; however, their regulatory roles in the translational control of gene expression in skeletal muscle remain to be defined. In a genetic screen to identify critical regulators of myogenesis, we identified a DEAD-Box RNA helicase, DDX27, that is required for skeletal muscle growth and regeneration. We demonstrate that DDX27 regulates ribosomal RNA (rRNA) maturation, and thereby the ribosome biogenesis and the translation of specific transcripts during myogenesis. These findings provide insight into the translational regulation of gene expression in myogenesis and suggest novel functions for ribosomes in regulating gene expression in skeletal muscles., Author summary Inherited skeletal muscle diseases are the most common form of genetic disorders with primary abnormalities in the structure and function of skeletal muscle resulting in the impaired locomotion in affected patients. A major hindrance to the development of effective therapies is a lack of understanding of biological processes that promote skeletal muscle growth. By performing a forward genetic screen in zebrafish we have identified mutation in a RNA helicase that leads to perturbations of ribosomal biogenesis pathway and impairs skeletal muscle growth and regeneration. Therefore, our studies have identified novel ribosome-based disease processes that may be therapeutic modulated to restore muscle function in skeletal muscle diseases.
- Published
- 2018