RT Journal Article
SR Electronic
T1 RNA helicase, DDX27 regulates proliferation and myogenic commitment of muscle stem cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 125484
DO 10.1101/125484
A1 Alexis H Bennett
A1 Marie-Francoise O’Donohue
A1 Stacey R. Gundry
A1 Aye T. Chan
A1 Jeffery Widrick
A1 Isabelle Draper
A1 Anirban Chakraborty
A1 Yi Zhou
A1 Leonard I. Zon
A1 Pierre-Emmanuel Gleizes
A1 Alan H. Beggs
A1 Vandana A Gupta
YR 2017
UL http://biorxiv.org/content/early/2017/04/07/125484.abstract
AB Developmental processes depend 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 and developmental processes. Ribosomes are a central component of the protein biosynthesis machinery in cells; however, their regulatory roles in the translational control of gene expression in an organ specific context during development 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 the proliferation and myogenic commitment of skeletal muscle stem cells. DDX27 deficient skeletal muscle exhibits hypotrophy and impaired regeneration potential. We demonstrate that DDX27 regulates ribosomal RNA (rRNA) maturation, and thereby the ribosome biogenesis and the translation of specific transcripts that are required to maintain pluripotency and myogenic differentiation of satellite cells. These findings provide insight into the translational regulation of gene expression in myogenesis and suggest novel functions for ribosomes in regulating gene expression during skeletal muscle development.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.