Investigation of Staufen1 Function in Myogenesis Highlights Multifunctionality and Complexity of Translational Regulation

Staufen is a double-stranded RNA binding protein (dsRBP) with discovered homologs in a diverse range of animals, insects, and other multicellular organisms. Staufen acts on secondary structures in mRNA transcripts to modulate translation of many targets through several mechanisms of action. It has roles in microtubule-dependent subcellular localization of mRNA transcripts, translational activation, transcript stability, Staufen-mediated mRNA decay (SMD), is a known component of RNA granules, and has been implicated in several cellular processes, one being myogenesis. Mammals have two Staufen orthologs–Staufen1 and Staufen2. Staufen1 has four conserved dsRNA binding domains (dsRBDs), each with distinct functional characteristics. This study finds that cultured MuSCs show distinct patterns of Staufen1 transcriptional expression from quiescence throughout the myogenic differentiation program characterized by high expression in quiescent satellite cells, less expression in proliferating myoblasts, and fairly high, sustained expression throughout differentiation and myotube formation. The temporal expression pattern is compared with recently reported novel Staufen1 functions in myogenesis. This research highlights that Staufen1 is able to act on transcripts in several overlapping ways to assist in the regulation of myogenesis, and more extensive characterization of Staufen1 as well as high-confidence identification of Staufen binding sites (SBS), will be necessary to fit Staufen1 into a model of translational regulation in myogenesis.