Characterizing ARS2 localization and function in differentiating myoblasts




Christie, Jennifer

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ARS2 is a member of the nuclear cap-binding complex (CBC) that is critical for a number of RNA processing pathways. The emerging model is that ARS2 acts as a master regulator of RNAPII transcript maturation by bringing capped RNA substrates together with the appropriate processing machinery. ARS2 is essential for early mammalian development but it remains unclear precisely how ARS2 functions in stem and progenitor cell maintenance and differentiation. The purpose of this study was to answer basic questions about the localization and function of ARS2 in muscle progenitor cells. Here I describe the localization of ARS2 in proliferating myoblasts and post-mitotic differentiating myotubes and show that disruption of ARS2 expression levels by knockdown or overexpression results in impaired myogenic differentiation. I also discovered a new isoform of ARS2 that is localized exclusively in the cytoplasm and found preliminary evidence that ARS2 is required for nonsense-mediated decay (NMD). This study includes the first evidence that an ARS2 isoform is expressed in the cytoplasm and opens the door for the discovery of new ARS2 functions beyond its reported roles in the nucleus.



myogenesis, nonsense-mediated decay, histone processing, ARS2