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

• Published in: PLoS pathogens 2017-08, Vol.13 (8), p.e1006593-e1006593
• Main Authors: Muller, Mandy, Glaunsinger, Britt A
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Abundance; Apoptosis; Biology and life sciences; Blotting, Western; Cell cycle; Cell Line; Cleavage; Cytokines; Degradation; Endonucleases - metabolism; Gene expression; Gene Expression Regulation; Herpes viruses; Herpesviridae Infections - virology; Herpesvirus 8, Human; Homology; Host-Pathogen Interactions - physiology; Humans; Immunoprecipitation; In Situ Hybridization, Fluorescence; Infections; Influenza; Interleukin 6; Interleukin-6 - metabolism; Medical research; Messenger RNA; Molecular biology; Nuclease; Nucleases; Nucleotide sequence; Open access; Pathogenesis; Physiological aspects; Polymerase Chain Reaction; Properties; Proteins; Quality control; Research and analysis methods; Ribonucleic acid; Ribonucleoproteins; RNA; RNA polymerase; RNA Stability - physiology; RNA, Messenger - metabolism; RNA-binding protein; Sarcoma; Transcription; Viral infections; Viruses
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1006593

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.