RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes
RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes
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 SUMMARYInherited 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.
Chan Aye T.、Widrick Jeffery、Draper Isabelle、Zhou Yi、Zon Leonard I.、Gleizes Pierre-Emmanuel、O?ˉDonohue Marie-Francoise、Beggs Alan H.、Gundry Stacey R.、Gupta Vandana A、Chakraborty Anirban、Bennett Alexis H
Stem Cell Program and Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical SchoolDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical SchoolMolecular Cardiology Research Institute, Tufts Medical CenterStem Cell Program and Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical SchoolStem Cell Program and Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School||Howard Hughes Medical InstituteLaboratoire de Biologie Mol¨|culaire Eucaryote, Centre de Biologie Int¨|grative (CBI), Universit¨| de ToulouseLaboratoire de Biologie Mol¨|culaire Eucaryote, Centre de Biologie Int¨|grative (CBI), Universit¨| de ToulouseDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical SchoolDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical SchoolDivision of Genetics, Brigham and Women?ˉs Hospital, Harvard Medical School||Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical SchoolLaboratoire de Biologie Mol¨|culaire Eucaryote, Centre de Biologie Int¨|grative (CBI), Universit¨| de Toulouse||Division of Molecular Genetics and Cancer, NU Centre for Science Education and Research, Nitte UniversityDivision of Genetics, Brigham and Women?ˉs Hospital, Harvard Medical School
基础医学分子生物学细胞生物学
Skeletal muscleMuscle precursor cellsmuscle stem cellssatellite cellsdifferentiationrRNA processingribosometranslational regulationgene expression
Chan Aye T.,Widrick Jeffery,Draper Isabelle,Zhou Yi,Zon Leonard I.,Gleizes Pierre-Emmanuel,O?ˉDonohue Marie-Francoise,Beggs Alan H.,Gundry Stacey R.,Gupta Vandana A,Chakraborty Anirban,Bennett Alexis H.RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes[EB/OL].(2025-03-28)[2025-04-27].https://www.biorxiv.org/content/10.1101/125484.点此复制
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