A conserved RNA processing pathway coordinates striated muscle development. Aaron N. Johnson^1,3, Mayssa M. Mokalled², Kenneth D. Poss², Eric N. Olson³. 1) Department of Integrative Biology, University of Colorado Denver, Denver, CO; 2) Department of Cell Biology and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC; 3) Department of Molecular Biology, UT Southwestern Medical Center at Dallas, Dallas, TX.

   Striated muscle differentiation requires the coordinated expression of arrays of genes involved in sarcomere formation and contractility. Although muscle structural genes are dispersed throughout the genome, sarcomeric proteins are somehow simultaneously assembled at specific subcellular locations through a largely unknown post-transcriptional mechanism. In a genetic screen for regulators of muscle development in Drosophila, we identified the RNA binding protein Hoi Polloi (Hoip). Remarkably, numerous sarcomeric proteins fail to be expressed in hoip mutant embryos even though the transcriptional activator of muscle structural genes, Mef2, is expressed at normal levels. Hoip physically interacts with multiple sarcomeric mRNAs and is required for their processing and nuclear export. In addition, the human Hoip orthologue NHP2L1 rescues muscle defects in hoip embryos, and knockdown of endogenous nhp2l1 in zebrafish blocks skeletal muscle differentiation. Thus, sarcomeric RNAs transcribed from dispersed genomic loci are co-regulated by a conserved regulatory network that directs the precise assembly of the contractile apparatus during myogenesis.