Evidence map›Paper›PMID 38815579›Full record

ArticleMolecular cell2024

hnRNPM protects against the dsRNA-mediated interferon response by repressing LINE-associated cryptic splicing.

Rong Zheng, Mikayla Dunlap, Georg O M Bobkov, Carlos Gonzalez-Figueroa, Khushali J Patel, Jingyi Lyu, Samuel E Harvey, Tracey W Chan, Giovanni Quinones-Valdez, Mudra Choudhury and 8 more

Abstract read
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

  1. Review
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  9. Review
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  13. Review
  14. Review
  15. RNA triggers chronic stress during neuronal aging.bioRxiv : the preprint server for biology · 2025
    Article
  16. Article
  17. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Rong ZhengLester & Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Mikayla DunlapLester & Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Georg O M BobkovLester & Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Carlos Gonzalez-FigueroaDepartment of Integrative Biology and Physiology and the Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Khushali J PatelLester & Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Jingyi LyuLester & Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Samuel E HarveyLester & Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Tracey W ChanBioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Giovanni Quinones-ValdezDepartment of Integrative Biology and Physiology and the Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Mudra ChoudhuryBioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Charlotte A Le RouxVerna & Marrs McLean Department of Biochemistry & Molecular Pharmacology and Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA.
Mason D BartelsVerna & Marrs McLean Department of Biochemistry & Molecular Pharmacology and Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA.
Amy VuongLester & Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Ryan A FlynnCenter for Personal Dynamic Regulome, Stanford University School of Medicine, Stanford, CA 94305, USA.
Howard Y ChangCenter for Personal Dynamic Regulome, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Eric L Van NostrandVerna & Marrs McLean Department of Biochemistry & Molecular Pharmacology and Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA.
Xinshu XiaoDepartment of Integrative Biology and Physiology and the Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: gxxiao@g.ucla.edu.
Chonghui ChengLester & Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: chonghui.cheng@bcm.edu.

Funding

LncRNA mechanisms in cancerR35CA209919 · NCI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2016 to 2022
$6.4M
Regulation of alternative splicing during epithelial-mesenchymal transitionR35GM131876 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI Chonghui Cheng · 2019 to 2026
$3.9M
Regulation and function of dsRNAs derived from retrotransposable elements in ADR01AG078950 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Xinshu Grace Xiao · 2022 to 2026
$3.2M
Systematic approaches to deciphering regulation and function of RNA editing in brainR01MH123177 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI XIAO, XINSHU GRACE · 2021 to 2025
$3.1M
Exploiting public genomic and transcriptomic data to uncover cancer-RNA editing relationshipsR01CA262686 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Xinshu Grace Xiao · 2022 to 2026
$1.9M
NCI NIH HHS R01 CA262686NCI NIH HHS R35 CA209919NIA NIH HHS R01 AG078950NIGMS NIH HHS R35 GM131876NIMH NIH HHS R01 MH123177
6 · The paper itself

Abstract

RNA splicing is pivotal in post-transcriptional gene regulation, yet the exponential expansion of intron length in humans poses a challenge for accurate splicing. Here, we identify hnRNPM as an essential RNA-binding protein that suppresses cryptic splicing through binding to deep introns, maintaining human transcriptome integrity. Long interspersed nuclear elements (LINEs) in introns harbor numerous pseudo splice sites. hnRNPM preferentially binds at intronic LINEs to repress pseudo splice site usage for cryptic splicing. Remarkably, cryptic exons can generate long dsRNAs through base-pairing of inverted ALU transposable elements interspersed among LINEs and consequently trigger an interferon response, a well-known antiviral defense mechanism. Significantly, hnRNPM-deficient tumors show upregulated interferon-associated pathways and elevated immune cell infiltration. These findings unveil hnRNPM as a guardian of transcriptome integrity by repressing cryptic splicing and suggest that targeting hnRNPM in tumors may be used to trigger an inflammatory immune response, thereby boosting cancer surveillance.

Indexed as

Heterogeneous-Nuclear Ribonucleoprotein Group MIntronsLong Interspersed Nucleotide ElementsRNA, Double-StrandedRNA SplicingAlu ElementsAnimalsExonsHEK293 CellsHumansInterferonsMiceRNA Splice SitesTranscriptomeHeterogeneous-Nuclear Ribonucleoprotein Group MHNRNPM protein, humanInterferonsRNA, Double-StrandedRNA Splice SitesALUcancercryptic splicingdouble-stranded RNAhnRNPMinterferon responseLINERNA-binding protein

Identifiers

PMID38815579
PMCPMC11204102

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.