Post-transcriptional regulation of myotube elongation and myogenesis by Hoi Polloi.
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.
Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, TX 75390-9148, USA. aaron.n.johnson@ucdenver.edu
Aaron N
AN
Johnson
Mayssa H
MH
Mokalled
Juliana M
JM
Valera
Kenneth D
KD
Poss
Eric N
EN
Olson
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D054792:Muscle, Striated / Q000196:embryology* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D018995:Myosin Heavy Chains / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism; D012518:Sarcomeres / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D014335:Tropomyosin / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology
D017931:DNA Primers; D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; C402291:Snu13 protein, human; D014335:Tropomyosin; C533658:hoip protein, Drosophila; D018995:Myosin Heavy Chains
Drosophila; Myogenesis; Myotube elongation; Post-transcriptional regulation; Zebrafish