Nuclease escape elements protect messenger RNA against cleavage by multiple viral endonucleases

PLoS Pathogens

Britt A. Glaunsinger¹  Mandy Muller¹ 

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

关键词: Messenger RNA;    3' UTR;    Small interfering RNAs;    293T cells;    Virus effects on host gene expression;    Nucleases;    Gene expression;    RNA stem-loop structure;   

DOI  :  10.1371/journal.ppat.1006593

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

During lytic Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, the viral endonu- clease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA). However, select mRNAs, including the transcript encoding interleukin-6 (IL-6), escape SOX-induced cleavage. IL-6 escape is mediated through a 3’ UTR RNA regulatory element that overrides the SOX targeting mechanism. Here, we reveal that this protective RNA element functions to broadly restrict cleavage by a range of homologous and non-homologous viral endonucleases. However, it does not impede cleavage by cellular endonucleases. The IL-6 protective sequence may be representative of a larger class of nuclease escape elements, as we identified a similar protective element in the GADD45B mRNA. The IL-6 and GADD45B-derived elements display similarities in their sequence, putative structure, and several associated RNA binding proteins. However, the overall composition of their ribonucleoprotein complexes appears distinct, leading to differences in the breadth of nucleases restricted. These findings highlight how RNA elements can selectively control transcript abundance in the background of widespread virus-induced mRNA degradation.

【 授权许可】

CC BY