Post-transcriptional regulation of myotube elongation and myogenesis by Hoi Polloi.

Published

Journal Article

Striated muscle development requires the coordinated expression of genes involved in sarcomere formation and contractility, as well as genes that determine muscle morphology. However, relatively little is known about the molecular mechanisms that control the early stages of muscle morphogenesis. To explore this facet of myogenesis, we performed a genetic screen for regulators of somatic muscle morphology in Drosophila, and identified the putative RNA-binding protein (RBP) Hoi Polloi (Hoip). Hoip is expressed in striated muscle precursors within the muscle lineage and controls two genetically separable events: myotube elongation and sarcomeric protein expression. Myotubes fail to elongate in hoip mutant embryos, even though the known regulators of somatic muscle elongation, target recognition and muscle attachment are expressed normally. In addition, a majority of sarcomeric proteins, including Myosin Heavy Chain (MHC) and Tropomyosin, require Hoip for their expression. A transgenic MHC construct that contains the endogenous MHC promoter and a spliced open reading frame rescues MHC protein expression in hoip embryos, demonstrating the involvement of Hoip in pre-mRNA splicing, but not in transcription, of muscle structural genes. In addition, the human Hoip ortholog NHP2L1 rescues muscle defects in hoip embryos, and knockdown of endogenous nhp2l1 in zebrafish disrupts skeletal muscle development. We conclude that Hoip is a conserved, post-transcriptional regulator of muscle morphogenesis and structural gene expression.

Full Text

Duke Authors

Cited Authors

  • Johnson, AN; Mokalled, MH; Valera, JM; Poss, KD; Olson, EN

Published Date

  • September 2013

Published In

Volume / Issue

  • 140 / 17

Start / End Page

  • 3645 - 3656

PubMed ID

  • 23942517

Pubmed Central ID

  • 23942517

Electronic International Standard Serial Number (EISSN)

  • 1477-9129

Digital Object Identifier (DOI)

  • 10.1242/dev.095596

Language

  • eng

Conference Location

  • England