Evidence map›Paper›PMID 42239063›Full record

ArticlebioRxiv : the preprint server for biology2026

A BRRF1-CCR4-NOT axis underlies conserved transcriptome-wide loss of splicing fidelity during gammaherpesvirus reactivation.

Trang T Nguyen, Anandita Ghosh, Nadeeshika Wickramarachchige-Dona, Tina M O'Grady, Claire Roberts, Eman Ishaq, Jordan Bass, Meggie Lam, Melody Baddoo, Nathan A Ungerleider and 8 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

18 authors.

Trang T NguyenDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Anandita GhoshDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Nadeeshika Wickramarachchige-DonaDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Tina M O'GradyPartner Therapeutics, Lexington, MA, USA.
Claire RobertsHaya Therapeutics, San Diego, CA, USA.
Eman IshaqDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Jordan BassDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Meggie LamDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Melody BaddooTulane Cancer Center, New Orleans, LA, USA.
Nathan A UngerleiderDepartment of Molecular Biology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA.
Nick Van OtterlooDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Jia WangDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Qian ZhangDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA.
Hong LiuDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA.ORCID 0000-0001-5038-3327
Yan DongDepartment of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA.
Rolf RenneDepartment of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA.
Truong D NguyenDepartment of Molecular, Cellular & Biomedical Sciences, City University of New York School of Medicine, New York, New York, USA.
Erik K FlemingtonDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA.

Funding

"Project 3" MHV68 IncRNA/miRNA interaction in latency and lympomagenesisP01CA214091 · NCI · UNIVERSITY OF FLORIDA · PI Scott A. Tibbetts · 2017 to 2026
$15.9M
Programmed splicing derangement as new EBV host cell shut-off mechanismR01CA262090 · NCI · WAYNE STATE UNIVERSITY · PI ERIK K FLEMINGTON · 2022 to 2026
$2.1M
EBV reactivation causes widespread host de novo promoter transcription and transcriptional interferenceR01CA272142 · NCI · WAYNE STATE UNIVERSITY · PI ERIK K FLEMINGTON · 2022 to 2026
$2.1M
RPMS1 circular RNAs in EBV malignanciesR01CA243793 · NCI · TULANE UNIVERSITY OF LOUISIANA · PI FLEMINGTON, ERIK K · 2019 to 2023
$1.8M
RNA-binding as a new paradigm for androgen receptor-mediated prostate cancer therapeutic resistanceR01CA301628 · NCI · WAYNE STATE UNIVERSITY · PI Yan Dong, ERIK K FLEMINGTON · 2025 to 2026
$1.3M
NCI NIH HHS P01 CA214091NCI NIH HHS R01 CA243793NCI NIH HHS R01 CA262090NCI NIH HHS R01 CA272142NCI NIH HHS R01 CA301628
6 · The paper itself

Abstract

Gammaherpesvirus reactivation drives a collapse of host mRNA splicing fidelity that extends across the transcriptome, with exon skipping affecting up to ~57% of expressed genes, exceeding the effects of depletion of any of 186 splicing factors. Combining five Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation systems across B cell and epithelial models with deep poly(A)+ RNA sequencing of purified lytic cells, we find that most induced isoforms are predicted to undergo nonsense-mediated decay or to lose conserved protein domains, broadly compromising cell cycle, innate immune and RNA-processing pathways. The phenotype arises independently of viral DNA replication, indicating early host remodeling. A screen of EBV early genes identifies BRRF1 as a key driver: through a CIY(Y/E) motif conserved in KSHV ORF49, BRRF1 engages the nuclear CCR4-NOT complex through its CNOT9 and CNOT1 subunits, hijacking this canonically cytoplasmic deadenylation hub for nuclear disruption of host splicing.

Identifiers

PMID42239063
PMCPMC13228557

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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.