Dual Short Upstream Open Reading Frames Control Translation of a Herpesviral Polycistronic mRNA

PLoS Pathogens

Jae U. Jung¹  Kevin F. Brulois¹  Britt A. Glaunsinger²  Lisa M. Kronstad² 

[1] Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America;Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, United States of America

关键词: Protein translation;    Messenger RNA;    Untranslated regions;    Kaposi's sarcoma-associated herpesvirus;    Internal ribosome entry site;    293T cells;    Northern blot;    Translation initiation;   

DOI  :  10.1371/journal.ppat.1003156

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY