The E3 SUMO ligase Nse2 regulates sumoylation and nuclear-to-cytoplasmic translocation of skNAC-Smyd1 in myogenesis

Skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide associated complex (skNAC) is exclusively found in striated muscle cells. Its function, however, is largely unknown. Previous reports could demonstrate that skNAC binds to Smyd1/m-Bop, a multi-functional protein regulating myogenesis both via the control of transcription and the modulation of sarcomerogenesis, and that both proteins undergo nuclear-to-cytoplasmic translocation at later stages of myogenic differentiation. Here, we show that skNAC binds to the E3 SUMO ligase mammalian Mms21/Nse2 and that knockdown of Nse2 expression inhibits specific aspects of myogenic differentiation, accompanied by a partial blockade of the nuclear-to-cytoplasmic translocation of the skNAC/Smyd1 complex, retention of the complex in PML-like nuclear bodies, and disturbed sarcomerogenesis. In addition, we show that the skNAC interaction partner Smyd1 contains a putative sumoylation motif and is sumoylated in muscle cells, with depletion of Mms21/Nse2 leading to reduced concentrations of sumoylated Smyd1. Taken together, our data suggest that the function, specifically the balance between nuclear and cytosolic roles of the skNAC/Smyd1 complex, might be regulated by sumoylation.