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PLoS Pathog. 2013 Jan;9(1):e1003156. doi: 10.1371/journal.ppat.1003156. Epub 2013 Jan 31.

Dual short upstream open reading frames control translation of a herpesviral polycistronic mRNA.

Author information

1
Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, United States of America.

Abstract

The Kaposi's sarcoma-associated herpesvirus (KSHV) protein kinase, encoded by ORF36, functions to phosphorylate cellular and viral targets important in the KSHV lifecycle and to activate the anti-viral prodrug ganciclovir. Unlike the vast majority of mapped KSHV genes, no viral transcript has been identified with ORF36 positioned as the 5'-proximal gene. Here we report that ORF36 is robustly translated as a downstream cistron from the ORF35-37 polycistronic transcript in a cap-dependent manner. We identified two short, upstream open reading frames (uORFs) within the 5' UTR of the polycistronic mRNA. While both uORFs function as negative regulators of ORF35, unexpectedly, the second allows for the translation of the downstream ORF36 gene by a termination-reinitiation mechanism. Positional conservation of uORFs within a number of related viruses suggests that this may be a common γ-herpesviral adaptation of a host translational regulatory mechanism.

PMID:
23382684
PMCID:
PMC3561293
DOI:
10.1371/journal.ppat.1003156
[Indexed for MEDLINE]
Free PMC Article

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