Rxivist logo

Mechanism and consequences of herpes simplex virus 1-mediated regulation of host mRNA alternative polyadenylation

By Yongsheng Shi, Xiuye Wang, Liang Liu, Adam W Whisnant, Thomas Hennig, Lara Djakovic, Nabila Haque, Cindy Bach, Rozanne Sandri-Goldin, Florian Erhard, Caroline Friedel, Lars Dölken

Posted 26 Nov 2020
bioRxiv DOI: 10.1101/2020.11.26.399626

Eukaryotic gene expression is extensively regulated by cellular stress and pathogen infections. We have previously shown that herpes simplex virus 1 (HSV-1) and several cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) in host genes and that the viral immediate early factor ICP27 plays an important role in HSV-1-induced DoTT. Here, we show that HSV-1 infection also leads to widespread changes in alternative polyadenylation (APA) of host mRNAs. In the majority of cases, polyadenylation shifts to upstream poly(A) sites (PAS), including many intronic PAS. Mechanistically, ICP27 contributes to HSV-1-mediated APA regulation. HSV-1- and ICP27-induced activation of intronic PAS is sequence-dependent and does not involve general inhibition of U1 snRNP. HSV1-induced intronic polyadenylation is accompanied by early termination of RNAPII. Finally, HSV-1-induced mRNAs polyadenylated at intronic PAS are exported into the cytoplasm while APA isoforms with extended 3 UTRs are sequestered in the nuclei, both preventing the expression of the full-length gene products. Together with other recent studies, our results suggest that viral infection and cellular stresses induce a multi-faceted host shutoff response that includes DoTT and changes in APA profiles.

Download data

  • Downloaded 205 times
  • Download rankings, all-time:
    • Site-wide: 120,734
    • In molecular biology: 3,570
  • Year to date:
    • Site-wide: 100,419
  • Since beginning of last month:
    • Site-wide: 80,042

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide