Evidence map›Paper›PMID 36460671›Full record

ArticleNature communications2022

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, Nicholas K Conrad

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Anne M DevlinDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA.
Ashutosh ShuklaDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA.
Julio C RuizDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA.
Spencer D BarnesLyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA.
Ashwin GovindanDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA.
Olga V HunterDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA.
Anna M ScarboroughDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA.
Iván D'OrsoDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-1409-2351
Nicholas K ConradDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA. Nicholas.Conrad@UTSouthwestern.edu.
Southwestern Medical Center · US

Funding

Transcriptional regulatory mechanisms shaping HIV proviral fateR01AI114362 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI D'ORSO, IVAN · 2015 to 2024
$4.6M
Mechanisms of KSHV posttranscriptional gene regulationR01AI123165 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI CONRAD, NICHOLAS K · 2016 to 2025
$4.5M
Mechanisms regulating KSHV transcription elongation and terminationR01AI153175 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI CONRAD, NICHOLAS K · 2021 to 2025
$2.3M
Transcriptional regulatory mechanisms shaping HIV proviral fateR37AI114362 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Ivan D'Orso · 2025 to 2026
$1.0M
NIAID NIH HHS R01 AI114362NIAID NIH HHS R01 AI123165NIAID NIH HHS R01 AI153175NIAID NIH HHS R37 AI114362U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI123165U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI153175
6 · The paper itself

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.

Indexed as

HerpesviridaeHerpesvirus 8, HumanMultiple MyelomaSarcoma, KaposiAnimalsMammalsNucleotidyltransferasesRNA, ViralTranscription, GeneticNucleotidyltransferasesRNA, Viral

Identifiers

PMID36460671
PMCPMC9718767
OpenAlexW4310576950

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.