Evidence map›Paper›PMID 37535888›Full record

ArticleHuman molecular genetics2023

Arginine methylation of RNA-binding proteins is impaired in Huntington's disease.

Tamara Ratovitski, Siddhi V Kamath, Robert N O'Meally, Keerthana Gosala, Chloe D Holland, Mali Jiang, Robert N Cole, Christopher A Ross

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. 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

8 authors at 1 institution in 3 countries.

Tamara RatovitskiDepartment of Psychiatry and Behavioral Sciences, Division of Neurobiology, Johns Hopkins University, Baltimore, MD 21287, USA.ORCID 0000-0003-4020-5644
Siddhi V KamathDepartment of Psychiatry and Behavioral Sciences, Division of Neurobiology, Johns Hopkins University, Baltimore, MD 21287, USA.
Robert N O'MeallyDepartment of Biological Chemistry, Mass Spectrometry and Proteomics Facility, Johns Hopkins University, Baltimore, MD 21287, USA.
Keerthana GosalaDepartment of Psychiatry and Behavioral Sciences, Division of Neurobiology, Johns Hopkins University, Baltimore, MD 21287, USA.
Chloe D HollandDepartment of Psychiatry and Behavioral Sciences, Division of Neurobiology, Johns Hopkins University, Baltimore, MD 21287, USA.
Mali JiangDepartment of Psychiatry and Behavioral Sciences, Division of Neurobiology, Johns Hopkins University, Baltimore, MD 21287, USA.
Robert N ColeDepartment of Biological Chemistry, Mass Spectrometry and Proteomics Facility, Johns Hopkins University, Baltimore, MD 21287, USA.
Christopher A RossDepartment of Psychiatry and Behavioral Sciences, Division of Neurobiology, Johns Hopkins University, Baltimore, MD 21287, USA.
Johns Hopkins University · US

Funding

Targeting Protein Arginine Methylation in HDR21NS109412 · NINDS · JOHNS HOPKINS UNIVERSITY · PI RATOVITSKI, TAMARA · 2019 to 2020
$450k
NIH HHS 5R21NS109412-02NINDS NIH HHS R21 NS109412
6 · The paper itself

Abstract

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the HD gene, coding for huntingtin protein (HTT). Mechanisms of HD cellular pathogenesis remain undefined and likely involve disruptions in many cellular processes and functions presumably mediated by abnormal protein interactions of mutant HTT. We previously found HTT interaction with several protein arginine methyl-transferase (PRMT) enzymes. Protein arginine methylation mediated by PRMT enzymes is an important post-translational modification with an emerging role in neurodegeneration. We found that normal (but not mutant) HTT can facilitate the activity of PRMTs in vitro and the formation of arginine methylation complexes. These interactions appear to be disrupted in HD neurons. This suggests an additional functional role for HTT/PRMT interactions, not limited to substrate/enzyme relationship, which may result in global changes in arginine protein methylation in HD. Our quantitative analysis of striatal precursor neuron proteome indicated that arginine protein methylation is significantly altered in HD. We identified a cluster highly enriched in RNA-binding proteins with reduced arginine methylation, which is essential to their function in RNA processing and splicing. We found that several of these proteins interact with HTT, and their RNA-binding and localization are affected in HD cells likely due to a compromised arginine methylation and/or abnormal interactions with mutant HTT. These studies reveal a potential new mechanism for disruption of RNA processing in HD, involving a direct interaction of HTT with methyl-transferase enzymes and modulation of their activity and highlighting methylation of arginine as potential new therapeutic target for HD.

Indexed as

ArginineHuntington DiseaseNerve Tissue ProteinsRNA-Binding ProteinsAnimalsHumansHuntingtin ProteinMethylationNeuronsProtein-Arginine N-MethyltransferasesProtein Processing, Post-TranslationalArginineHTT protein, humanHuntingtin ProteinNerve Tissue ProteinsProtein-Arginine N-MethyltransferasesRNA-Binding Proteins

Identifiers

PMID37535888
PMCPMC10549789
OpenAlexW4385515918

What OpenQuestion holds

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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 OpenQuestion graph.