Title | RNA decay during gammaherpesvirus infection reduces RNA polymerase II occupancy of host promoters but spares viral promoters. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Hartenian, E, Gilbertson, S, Federspiel, JD, Cristea, IM, Glaunsinger, BA |
Journal | PLoS Pathog |
Volume | 16 |
Issue | 2 |
Pagination | e1008269 |
Date Published | 2020 02 |
ISSN | 1553-7374 |
Keywords | Animals, Endonucleases, Genome, Viral, Herpesviridae Infections, Herpesvirus 8, Human, Mice, NIH 3T3 Cells, Promoter Regions, Genetic, Rhadinovirus, RNA Polymerase II, RNA Stability, Transcription Factor TFIIB, Viral Proteins, Virus Replication |
Abstract | <p>In mammalian cells, widespread acceleration of cytoplasmic mRNA degradation is linked to impaired RNA polymerase II (Pol II) transcription. This mRNA decay-induced transcriptional repression occurs during infection with gammaherpesviruses including Kaposi's sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68), which encode an mRNA endonuclease that initiates widespread RNA decay. Here, we show that MHV68-induced mRNA decay leads to a genome-wide reduction of Pol II occupancy at mammalian promoters. This reduced Pol II occupancy is accompanied by down-regulation of multiple Pol II subunits and TFIIB in the nucleus of infected cells, as revealed by mass spectrometry-based global measurements of protein abundance. Viral genes, despite the fact that they require Pol II for transcription, escape transcriptional repression. Protection is not governed by viral promoter sequences; instead, location on the viral genome is both necessary and sufficient to escape the transcriptional repression effects of mRNA decay. We propose a model in which the ability to escape from transcriptional repression is linked to the localization of viral DNA within replication compartments, providing a means for these viruses to counteract decay-induced transcript loss.</p> |
DOI | 10.1371/journal.ppat.1008269 |
Alternate Journal | PLoS Pathog |
PubMed ID | 32032393 |
PubMed Central ID | PMC7032723 |
Grant List | R01 CA136367 / CA / NCI NIH HHS / United States R01 GM114141 / GM / NIGMS NIH HHS / United States S10 OD018174 / OD / NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States |