The PNUTS-PP1 complex acts as an intrinsic barrier to herpesvirus KSHV gene expression and replication

Anne M. Devlin, Ashutosh Shukla, Julio C. Ruiz, Spencer D. Barnes, Ashwin Govindan, Olga V. Hunter, Anna M. Scarborough, Iván D’Orso and Nicholas K. Conrad ()
Additional contact information
Anne M. Devlin: UT Southwestern Medical Center
Ashutosh Shukla: UT Southwestern Medical Center
Julio C. Ruiz: UT Southwestern Medical Center
Spencer D. Barnes: UT Southwestern Medical Center
Ashwin Govindan: UT Southwestern Medical Center
Olga V. Hunter: UT Southwestern Medical Center
Anna M. Scarborough: UT Southwestern Medical Center
Iván D’Orso: UT Southwestern Medical Center
Nicholas K. Conrad: UT Southwestern Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Control of RNA Polymerase II (pol II) elongation is a critical component of gene expression in mammalian cells. The PNUTS-PP1 complex controls elongation rates, slowing pol II after polyadenylation sites to promote termination. The Kaposi’s sarcoma-associated herpesvirus (KSHV) co-opts pol II to express its genes, but little is known about its regulation of pol II elongation. We identified PNUTS as a suppressor of a KSHV reporter gene in a genome-wide CRISPR screen. PNUTS depletion enhances global KSHV gene expression and overall viral replication. Mechanistically, PNUTS requires PP1 interaction, binds viral RNAs downstream of polyadenylation sites, and restricts transcription readthrough of viral genes. Surprisingly, PNUTS also represses productive elongation at the 5´ ends of the KSHV reporter and the KSHV T1.4 RNA. From these data, we conclude that PNUTS’ activity constitutes an intrinsic barrier to KSHV replication likely by suppressing pol II elongation at promoter-proximal regions.

Date: 2022
References: View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-35268-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35268-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-35268-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().