Alphavirus nsP3 ADP-ribosylhydrolase Activity Disrupts Stress Granule Formation

Aravinth Kumar Jayabalan; Diane E. Griffin; Anthony K. L. Leung

Expression of FUS R495X in neuronal cells is reported to cause the dispersion of the protein COPBI-the coatomer beta subunit of the coat protein complex I involved in retrograde vesicular trafficking from Golgi and ER [61] . Intriguingly, expression of nsP3 WT, but not the G32E mutant, restored the dispersed pattern of COPBI in FUS R495X-transfected neuronal SH-SY5Y cells to the compact, juxtanuclear pattern observed in untransfected cells (Fig. 3f) . As in U2OS, SG-like aggregates were induced by the expression of FUS R495X in these neuronal cells (Fig. S4e-f) , and the number of aggregates were reduced upon co-transfection with nsP3 WT, but not G32E mutant (Fig. S4e-f ). These data further suggest that the nsP3 ADP-ribosylhydrolase activity restores at least one cellular property disrupted by the FUS R495X mutant in addition to SG disassembly.