Aberrant herpesvirus-induced polyadenylation correlates with cellular messenger RNA destruction

TitleAberrant herpesvirus-induced polyadenylation correlates with cellular messenger RNA destruction
Publication TypeJournal Article
Year of Publication2009
AuthorsLee YJ, Glaunsinger BA
JournalPLoS biology
Volume7
Issue5
Paginatione1000107
Date Published2009 May 5
ISSN1545-7885
KeywordsCell Line, Fluorescent Antibody Technique, Herpesvirus 8, Human, Humans, In Situ Hybridization, Polyadenylation, Polymerase Chain Reaction, RNA Stability, RNA, Messenger, Viral Proteins
AbstractRegulation of messenger RNA (mRNA) stability plays critical roles in controlling gene expression, ensuring transcript fidelity, and allowing cells to respond to environmental cues. Unregulated enhancement of mRNA turnover could therefore dampen cellular responses to such signals. Indeed, several herpesviruses instigate widespread destruction of cellular mRNAs to block host gene expression and evade immune detection. Kaposi's sarcoma-associated herpesvirus (KSHV) promotes this phenotype via the activity of its viral SOX protein, although the mechanism of SOX-induced mRNA turnover has remained unknown, given its apparent lack of intrinsic ribonuclease activity. Here, we report that KSHV SOX stimulates cellular transcriptome turnover via a unique mechanism involving aberrant polyadenylation. Transcripts in SOX-expressing cells exhibit extended poly(A) polymerase II-generated poly(A) tails and polyadenylation-linked mRNA turnover. SOX-induced polyadenylation changes correlate with its RNA turnover function, and inhibition of poly(A) tail formation blocks SOX activity. Both nuclear and cytoplasmic poly(A) binding proteins are critical cellular cofactors for SOX function, the latter of which undergoes striking nuclear relocalization by SOX. SOX-induced mRNA turnover therefore represents both a novel mechanism of host shutoff as well as a new model system to probe the regulation of poly(A) tail-stimulated mRNA turnover in mammalian cells.
DOI10.1371/journal.pbio.1000107
Alternate JournalPLoS Biol.