Evidence map›Paper›PMID 41115859›Full record

ArticleNature communications2025

Enhanced hybridization-proximity labeling discovers protein interactomes of single RNA molecules.

Karen Yap, Tek Hong Chung, Erin C Hedges, Agnes L Nishimura, Christopher E Shaw, Eugene V Makeyev

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. A unified photosensitizer platform forbioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. 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

6 authors.

Karen Yap *Centre for Developmental Neurobiology, King's College London, London, UK.ORCID http://orcid.org/0000-0002-0182-4795
Tek Hong Chung *Centre for Developmental Neurobiology, King's College London, London, UK.ORCID http://orcid.org/0000-0002-9572-8023
Erin C HedgesMaurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Agnes L NishimuraMaurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Christopher E ShawMaurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Eugene V MakeyevCentre for Developmental Neurobiology, King's College London, London, UK. eugene.makeyev@kcl.ac.uk.ORCID http://orcid.org/0000-0001-6034-6896

Funding

Motor Neurone Disease Association (MNDA) Nishimura/Dec20/942-793Motor Neurone Disease Association (MNDA) Shaw/Mar19/893-792RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/R001049/1RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/V006258/1RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/Y009304/1RCUK | Medical Research Council (MRC) MR/Z506187/1
6 · The paper itself

Abstract

RNAs engage diverse protein partners and localize to specific subcellular compartments, yet dissecting proteomes associated with low-abundance or dispersed RNA molecules remains a challenge. We present an enhanced hybridization-proximity labeling (HyPro) technology for in situ proteome profiling of endogenously expressed RNA microcompartments. We re-engineer the HyPro enzyme and optimize proximity biotinylation conditions to identify proteins associated with compact RNA-containing nuclear bodies, small pre-mRNA clusters, and individual transcripts. Applying this approach to pathogenic G4C2 repeat-containing C9orf72 RNAs, retained as single-molecule foci in the nuclei of amyotrophic lateral sclerosis (ALS) patient-derived pluripotent stem cells, we reveal extensive interactions with disease-linked paraspeckle markers and a specific set of pre-mRNA splicing factors. These findings highlight early RNA processing and localization defects in ALS that may contribute to this late-onset neurodegenerative disorder. Overall, HyPro provides a broadly applicable platform for mapping RNA-protein interactions, enabling insights into RNA biology and its dysregulation in disease.

Indexed as

RNAAmyotrophic Lateral SclerosisBiotinylationC9orf72 ProteinCell NucleusHumansPluripotent Stem CellsProteomeRNA-Binding ProteinsRNA PrecursorsC9orf72 ProteinC9orf72 protein, humanProteomeRNARNA-Binding ProteinsRNA Precursors

Identifiers

PMID41115859
PMCPMC12537909

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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.