Evidence map›Paper›PMID 40304179›Full record

ArticleNucleic acids research2025

PRMT5 promotes full-length HTT expression by repressing multiple proximal intronic polyadenylation sites.

Manisha Yadav, Mona A AlQazzaz, Felipe E Ciamponi, Jolene C Ho, Maxim I Maron, Aiden M Sababi, Graham MacLeod, Moloud Ahmadi, Garrett Bullivant, Vincent Tano and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

30 authors.

Manisha YadavDepartment of Medical Biophysics, University of Toronto, Toronto, ON, M5G1L7, Canada.ORCID 0000-0001-6559-7774
Mona A AlQazzazStructural Genomics Consortium, University of Toronto, Toronto, ON, M5G1L7, Canada.
Felipe E CiamponiCenter for Molecular Biology and Genetic Engineering, University of Campinas (UNICAMP), Campinas 13083-872, Brazil.ORCID 0000-0002-0076-8824
Jolene C HoStructural Genomics Consortium, University of Toronto, Toronto, ON, M5G1L7, Canada.
Maxim I MaronDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States.
Aiden M SababiDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S3E1, Canada.
Graham MacLeodDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S3E1, Canada.
Moloud AhmadiLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S3M2, Canada.
Garrett BullivantDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON, M5G0A4, Canada.
Vincent TanoLee Kong Chian School of Medicine, Nanyang Technological University, 636921, Singapore.
Sarah R LangleyLee Kong Chian School of Medicine, Nanyang Technological University, 636921, Singapore.
María Sánchez-OsunaInstitute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC, H3C3J7, Canada.
Patty SachamitrDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON, M5G0A4, Canada.
Michelle KushidaDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON, M5G0A4, Canada.
Costanza Ferrari BardileDepartment of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Djavad Mowafaghian Centre for Brain Health, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z4H4, Canada.
Mahmoud A PouladiDepartment of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Djavad Mowafaghian Centre for Brain Health, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z4H4, Canada.
Rebecca KurtzDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N3Z5, Canada.
Laura RichardsDepartment of Medical Biophysics, University of Toronto, Toronto, ON, M5G1L7, Canada.
Trevor PughDepartment of Medical Biophysics, University of Toronto, Toronto, ON, M5G1L7, Canada.ORCID 0000-0002-8073-5888
Mike TyersInstitute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC, H3C3J7, Canada.
Stephane AngersDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S3E1, Canada.
Peter B DirksDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON, M5G0A4, Canada.
Gary D BaderPrincess Margaret Cancer Centre, U niversity Health Network, Toronto, ON, M5G1L7, Canada.ORCID 0000-0003-0185-8861
Ray TruantDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N3Z5, Canada.ORCID 0000-0003-2542-6641
Katlin B MassirerCenter for Molecular Biology and Genetic Engineering, University of Campinas (UNICAMP), Campinas 13083-872, Brazil.ORCID 0000-0001-6390-2560
Dalia Barsyte-LovejoyStructural Genomics Consortium, University of Toronto, Toronto, ON, M5G1L7, Canada.ORCID 0000-0002-6560-9621
David ShechterDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States.
Rachel J HardingStructural Genomics Consortium, University of Toronto, Toronto, ON, M5G1L7, Canada.
Cheryl H ArrowsmithDepartment of Medical Biophysics, University of Toronto, Toronto, ON, M5G1L7, Canada.
Panagiotis PrinosStructural Genomics Consortium, University of Toronto, Toronto, ON, M5G1L7, Canada.ORCID 0000-0001-8785-7856

Funding

PRMT5-MEP50 Histone Arginine Methylation in Early DevelopmentR01GM108646 · NIGMS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI SHECHTER, DAVID · 2014 to 2022
$3.2M
American Association for Cancer ResearchBayer AGBoehringer IngelheimBristol Myers SquibbCanadian Institute of Health Research 142434Entertainment Industry FoundationGenentechGenome CanadaGovernment of OntarioIrma T. Hirschl TrustJanssenMerck KGaAMITACSNIGMS NIH HHS R01 GM108646NIH HHS R01GM108646Ontario Genomics Institute OGI-196Ontario Institute for Cancer ResearchPfizerPrincess Margaret Postdoctoral FellowshipStand Up to Cancer Canada SU2C-AACR-DT-19-15Structural Genomics ConsortiumTakeda
6 · The paper itself

Abstract

Expansion of the CAG trinucleotide repeat tract in exon 1 of the Huntingtin (HTT) gene causes Huntington's disease (HD) through the expression of a polyglutamine-expanded form of the HTT protein. This mutation triggers cellular and biochemical pathologies, leading to cognitive, motor, and psychiatric symptoms in HD patients. Targeting HTT splicing with small molecule drugs is a compelling approach to lowering HTT protein levels to treat HD, and splice modulators are currently being tested in the clinic. Here, we identify PRMT5 as a novel regulator of HTT messenger RNA (mRNA) splicing and alternative polyadenylation. PRMT5 inhibition disrupts the splicing of HTT introns 9 and 10, leading to the activation of multiple proximal intronic polyadenylation sites within these introns and promoting premature termination, cleavage, and polyadenylation of the HTT mRNA. This suggests that HTT protein levels may be lowered due to this mechanism. We also detected increasing levels of these truncated HTT transcripts across a series of neuronal differentiation samples, which correlated with lower PRMT5 expression. Notably, PRMT5 inhibition in glioblastoma stem cells potently induced neuronal differentiation. We posit that PRMT5-mediated regulation of intronic polyadenylation, premature termination, and cleavage of the HTT mRNA modulates HTT expression and plays an important role during neuronal differentiation.

Indexed as

Huntingtin ProteinIntronsPolyadenylationProtein-Arginine N-MethyltransferasesAlternative SplicingAnimalsCell DifferentiationCell Line, TumorHumansHuntington DiseaseNeuronsRNA, MessengerHTT protein, humanHuntingtin ProteinPRMT5 protein, humanProtein-Arginine N-MethyltransferasesRNA, Messenger

Identifiers

PMID40304179
PMCPMC12041856

What OpenQuestion holds

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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.