Fig. 9.

HeV M protein disrupts the Treacle–NBS1 complex. a HEK-293T cells co-transfected to express the indicated mCherry (mCh) protein with NBS1-GFP were subjected to IP for NBS1-GFP followed by analysis by IB using the indicated antibodies; results are representative of 3 independent experiments. b Models for (left panel) DDR-mediated and (right panel) HeV M protein-mediated inhibition of rRNA synthesis. Treacle is required for basal rRNA synthesis and localizes to Treacle-enriched subnucleolar compartments which appear to correspond to FC/DFC. (Left panel) During the DDR, Treacle function is inhibited by NBS1, with which Treacle forms a complex. (Right panel) During HeV infection, HeV M localizes to FC/DFC and binds to Treacle resulting in inhibition of Treacle-dependent function independently of a DDR; the capacity of M protein to disrupt the complex (a) suggests that it binds at or close to the Treacle–NBS1 interaction site to mimic a DDR-activated NBS1–Treacle complex