EndoU targets in MHV RNA. MHV RNA was targeted for cleavage by EndoU within infected BMM. MHV RNA was cleaved by EndoU in all regions of the genome, at C↓A and U↓A sequences. Because MHV RNA is a template for both viral mRNA translation and viral RNA replication, cleavage by EndoU could inhibit both of these biosynthetic processes. Intriguingly, MHV TRS sequences contain EndoU target sequences (C↓A and U↓A sequences). TRS6, which was targeted more frequently by EndoU than other TRS elements, contains a C↓A target sequence rather than a U↓A sequence. We postulate that EndoU cleaves MHV RNA in a regulated manner, to inhibit negative-strand RNA synthesis, thereby inhibiting the accumulation of viral dsRNA. Nsp16 (2′-O-MT) could regulate EndoU-mediated cleavage of MHV RNA by methylating C↓A and U↓A sequences. EndoU and RNase L cleave an overlapping set of UA sequences within MHV, suggesting a functional interplay between host and viral endoribonucleases.
