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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Anne M. Devlin & Ashutosh Shukla & Julio C. Ruiz & Spencer D. Barnes & Ashwin Govindan & Olga V. Hunter & Anna M. Scarborough & Iván D’Orso & Nicholas K. Conrad, 2022. "The PNUTS-PP1 complex acts as an intrinsic barrier to herpesvirus KSHV gene expression and replication," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35268-4
    DOI: 10.1038/s41467-022-35268-4
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