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Viruses 2015, 7(2), 496-510; doi:10.3390/v7020496

Multiple Regions of Kaposi’s Sarcoma-Associated Herpesvirus ORF59 RNA are Required for Its Expression Mediated by Viral ORF57 and Cellular RBM15

1
Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 1050 Boyles Street, Frederick, MD 21702, USA
2
Biostatistics & Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Current address: Molecular Biology and Biochemistry Department, University of California Irvine, Irvine, CA 92697, USA
Current address: JK BioPharma Solutions, Inc., Rockville, MD 20850, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Received: 19 December 2014 / Revised: 15 January 2015 / Accepted: 28 January 2015 / Published: 3 February 2015
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus)
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Abstract

KSHV ORF57 (MTA) promotes RNA stability of ORF59, a viral DNA polymerase processivity factor. Here, we show that the integrity of both ORF59 RNA ends is necessary for ORF57-mediated ORF59 expression and deletion of both 5’ and 3’ regions, or one end region with a central region, of ORF59 RNA prevents ORF57-mediated translation of ORF59. The ORF59 sequence between nt 96633 and 96559 resembles other known MTA-responsive elements (MREs). ORF57 specifically binds to a stem-loop region from nt 96596–96572 of the MRE, which also binds cellular RBM15. Internal deletion of the MRE from ORF59 led to poor export, but accumulation of nuclear ORF59 RNA in the presence of ORF57 or RBM15. Despite of being translatable in the presence of ORF57, this deletion mutant exhibits translational defect in the presence of RBM15. Together, our results provide novel insight into the roles of ORF57 and RBM15 in ORF59 RNA accumulation and protein translation. View Full-Text
Keywords: KSHV; ORF59; ORF57; RNA accumulation; RNA export; RBM15 KSHV; ORF59; ORF57; RNA accumulation; RNA export; RBM15
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Massimelli, M.J.; Majerciak, V.; Kang, J.-G.; Liewehr, D.J.; Steinberg, S.M.; Zheng, Z.-M. Multiple Regions of Kaposi’s Sarcoma-Associated Herpesvirus ORF59 RNA are Required for Its Expression Mediated by Viral ORF57 and Cellular RBM15. Viruses 2015, 7, 496-510.

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