Evidence map›Paper›PMID 39180495›Full record

ArticleHuman molecular genetics2024

Expression levels of core spliceosomal proteins modulate the MBNL-mediated spliceopathy in DM1.

Jiss M Louis, Jesus A Frias, Jacob H Schroader, Lindsey A Jones, Emily E Davey, Claudia D Lennon, Jacob Chacko, John D Cleary, J Andrew Berglund, Kaalak Reddy

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
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

10 authors.

Jiss M LouisThe RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.
Jesus A FriasThe RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.
Jacob H SchroaderThe RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.
Lindsey A JonesThe RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.
Emily E DaveyThe RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.
Claudia D LennonThe RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.
Jacob ChackoThe RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.
John D ClearyThe RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.ORCID 0000-0001-7599-5995
J Andrew BerglundThe RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.
Kaalak ReddyThe RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.ORCID 0000-0002-1916-0261

Funding

Senator Paul D. Wellstone Muscular Dystrophy Specialized Research CenterP50NS048843 · NINDS · UNIVERSITY OF ROCHESTER · PI THORNTON, CHARLES A · 2018 to 2022
$7.1M
Design, Synthesis and Efficacy of New Small Molecule Therapeutics to Impede Myotonic DystrophyR01NS120485 · NINDS · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI Andrew Berglund, Masayuki Nakamori · 2022 to 2026
$2.7M
RNA Science and Technology in Health and DiseaseT32GM132066 · NIGMS · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI Thomas J Begley · 2019 to 2026
$1.8M
Department of Defense HT94252410191NIGMS NIH HHS T32 GM132066NIH Diversity Supplement P50NS048843-20S1NIH HHS R01NS120485NIH T32 5T32GM132066NINDS NIH HHS P50 NS048843NINDS NIH HHS R01 NS120485
6 · The paper itself

Abstract

Myotonic dystrophy type 1 (DM1) is a heterogeneous multisystemic disease caused by a CTG repeat expansion in DMPK. Transcription of the expanded allele produces toxic CUG repeat RNA that sequesters the MBNL family of alternative splicing (AS) regulators into ribonuclear foci, leading to pathogenic mis-splicing. To identify genetic modifiers of toxic CUG RNA levels and the spliceopathy, we performed a genome-scale siRNA screen using an established HeLa DM1 repeat-selective screening platform. We unexpectedly identified core spliceosomal proteins as a new class of modifiers that rescue the spliceopathy in DM1. Modest knockdown of one of our top hits, SNRPD2, in DM1 fibroblasts and myoblasts, significantly reduces DMPK expression and partially rescues MBNL-regulated AS dysfunction. While the focus on the DM1 spliceopathy has centered around the MBNL proteins, our work reveals an unappreciated role for MBNL:spliceosomal protein stoichiometry in modulating the spliceopathy, revealing new biological and therapeutic avenues for DM1.

Indexed as

Alternative SplicingMyotonic DystrophyRNA-Binding ProteinsSpliceosomesFibroblastsHeLa CellsHumansMyotonin-Protein KinaseRNA, Small InterferingRNA SplicingTrinucleotide Repeat ExpansionDMPK protein, humanMBNL1 protein, humanMyotonin-Protein KinaseRNA-Binding ProteinsRNA, Small Interferingalternative splicinggenetic modifiersgenome screenmyotonic dystrophyrepeat expansion diseases

Identifiers

PMID39180495
PMCPMC11540926

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.