a viral nuclear noncoding rna binds re-localized poly(a) binding protein and is required for late kshv gene expression病毒核非编码rna结合re-localized保利(a)kshv后期需要结合蛋白和基因表达.pdfVIP

A Viral Nuclear Noncoding RNA Binds Re-localized Poly(A) Binding Protein and Is Required for Late KSHV Gene Expression 1 ` 2 1 3 1 Sumit Borah , Nicole Darricarrere , Alicia Darnell , Jinjong Myoung , Joan A. Steitz * 1 Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, United States of America, 2 Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, United States of America, 3 Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, California, United States of America Abstract During the lytic phase of infection, the gamma herpesvirus Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) expresses a highly abundant, 1.1 kb nuclear noncoding RNA of unknown function. We observe that this polyadenylated nuclear (PAN) RNA avidly binds host poly(A)-binding protein C1 (PABPC1), which normally functions in the cytoplasm to bind the poly(A) tails of mRNAs, regulating mRNA stability and translation efficiency. During the lytic phase of KSHV infection, PABPC1 is re- localized to the nucleus as a consequence of expression of the viral shutoff exonuclease (SOX) protein; SOX also mediates the host shutoff effect in which host mRNAs are downregulated while viral mRNAs are selectively expressed. We show that whereas PAN RNA is not required for the host shutoff effect or for PABPC1 re-localization, SOX strongly upregulates the levels of PAN RNA in transient transfection experiments. This upregulation is destroyed by the same SOX mutation that ablates the host shutoff effect and PABPC1 nuclear re-localization or by removal of the poly(A) tail of PAN. In cells induced into the KSHV lytic phase, depletion