The RNA Surveillance Factor UPF1 Represses Myogenesis via Its E3 Ubiquitin Ligase Activity

5 years ago

The RNA Surveillance Factor UPF1 Represses Myogenesis via Its E3 Ubiquitin Ligase Activity

UPF1 is an RNA helicase that orchestrates nonsense-mediated decay and other RNA surveillance pathways. While UPF1 is best known for its basal cytoprotective role in degrading aberrant RNAs, UPF1 also degrades specific, normally occurring mRNAs to regulate diverse cellular processes. Here we describe a role for UPF1 in regulated protein decay, wherein UPF1 acts as an E3 ubiquitin ligase to repress human skeletal muscle differentiation. Suppressing UPF1 accelerates myogenesis, while ectopically increasing UPF1 levels slows myogenesis. UPF1 promotes the decay of MYOD protein, a transcription factor that is a master regulator of myogenesis, while leaving MYOD mRNA stability unaffected. UPF1 acts as an E3 ligase via its RING domain to promote MYOD protein ubiquitination and degradation. Our data characterize a regulatory role for UPF1 in myogenesis, and they demonstrate that UPF1 provides a mechanistic link between the RNA and protein decay machineries in human cells.

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Teaser

Feng et al. report that UPF1, a core RNA surveillance factor, represses human skeletal myogenesis. UPF1’s repressive role in myogenesis is not explained by its well-studied RNA helicase activity. Instead, UPF1 has E3 ubiquitin ligase activity that targets MYOD protein, a master regulator of the myogenic process, for degradation.

Publisher URL: www.sciencedirect.com/science

DOI: S1097276517303982