Lymphotropic Herpesvirus saimiri Uses the SMN Complex To Assemble Sm Cores on Its Small RNAs

Abstract

The lymphotropic Herpesvirus saimiri (HVS) causes acute leukemia, T-cell lymphoma, and death in New World monkeys. HVS encodes seven small RNAs (HSURs) of unknown function. The HSURs acquire host Sm proteins and assemble Sm cores similar to those found on the spliceosomal small nuclear RNPs (snRNPs). Here we show that, like host snRNPs, HSURs use the SMN (survival of motor neurons) complex to assemble Sm cores. The HSURs bind the SMN complex directly and with very high affinity, similar to or higher than that of host snRNAs, and can outcompete host snRNAs for SMN-dependent assembly into RNPs. These observations highlight the general utility of the SMN complex for RNP assembly and suggest that infectious agents that engage the SMN complex may burden SMN-dependent pathways, possibly leading to a deleterious reduction in available SMN complex for essential host functions.

ACKNOWLEDGMENTS

We are grateful to Ronald C. Desrosiers and Joan A. Steitz for generously providing constructs for HVS and the HSURs. We thank the members of our laboratory, especially Amelie Gubitz, for helpful discussions and comments on the manuscript and Jin Wang for providing S5 cells. We are also grateful to Gina Daly for secretarial assistance.

This study was supported by the Association Française Contre les Myopathies and by a grant from the National Institute of Health. T.J.G. is a Predoctoral Fellow of the Howard Hughes Medical Institute. G.D. is an Investigator of the Howard Hughes Medical Institute.