Evidence map›Paper›PMID 34297914›Full record

ReviewNeuron2021

RNA modulates physiological and neuropathological protein phase transitions.

Jacob R Mann, Christopher J Donnelly

Open access · greenAbstract readReview
In one paragraph

Review in Neuron, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

42 citing papers in PubMed, 72 citations in OpenAlex.

  1. Article
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  15. Review
  16. Coding relationship links RNA G-quadruplexes and protein RGG motifs in RNA-binding protein autoregulation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. Review
  18. Article
  19. Biomolecular condensates and disease pathogenesis.Science China. Life sciences · 2024
    Review
  20. 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

2 authors at 1 institution in 1 country.

Jacob R MannCenter for Neuroscience, University of Pittsburgh, Pittsburgh, PA 15213, USA; LiveLikeLouCenter for ALS Research, University of Pittsburgh Brain Institute, Pittsburgh, PA 15213, USA; Center for Protein Conformational Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Christopher J DonnellyCenter for Neuroscience, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; LiveLikeLouCenter for ALS Research, University of Pittsburgh Brain Institute, Pittsburgh, PA 15213, USA; Center for Protein Conformational Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USA; Pittsburgh Institute for Neurodegeneration, University of Pittsburgh, Pittsburgh PA 15213. Electronic address: cjdon25@pitt.edu.
University of Pittsburgh · US

Funding

General Motor Control Mechanisms and Disease Training ProgramT32NS041234 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BEVAN, MARK D · 2001 to 2022
$6.0M
An optogenetic approach to establish the interplay between stress granules and TDP-43 proteinopathy in ALS/FTDR01NS105756 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DONNELLY, CHRISTOPHER JAMES · 2018 to 2022
$1.8M
Cell competition as a novel aspect of cellular senescence during agingR21AG067201 · NIA · BUCK INSTITUTE FOR RESEARCH ON AGING · PI CAMPISI, JUDITH · 2020 to 2021
$534k
Oligonucleotide approach to antagonize neurotoxic TDP-43 assemblies in dementiaR21AG064940 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DONNELLY, CHRISTOPHER JAMES, PANDEY, UDAI B · 2019 to 2020
$417k
NIA NIH HHS L30 AG048607NIA NIH HHS R21 AG064940NIA NIH HHS R21 AG067201NINDS NIH HHS R01 NS105756NINDS NIH HHS T32 NS041234
6 · The paper itself

Abstract

Aggregation of RNA-binding proteins (RBPs) is a pathological hallmark of neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In these diseases, TDP-43 and FUS RBPs are depleted from the nuclear compartment, where they are normally localized, and found within cytoplasmic inclusions in degenerating regions of affected individuals' postmortem tissue. The mechanisms responsible for aggregation of these proteins has remained elusive, but recent studies suggest liquid-liquid phase separation (LLPS) might serve as a critical nucleation step in formation of pathological inclusions. The process of phase separation also underlies the formation and maintenance of several functional membraneless organelles (MLOs) throughout the cell, some of which contain TDP-43, FUS, and other disease-linked RBPs. One common ligand of disease-linked RBPs, RNA, is a major component of MLOs containing RBPs and has been demonstrated to be a strong modulator of RBP phase transitions. Although early evidence suggested a largely synergistic effect of RNA on RBP phase separation and MLO assembly, recent work indicates that RNA can also antagonize RBP phase behavior under certain physiological and pathological conditions. In this review, we describe the mechanisms underlying RNA-mediated phase transitions of RBPs and examine the molecular properties of these interactions, such as RNA length, sequence, and secondary structure, that mediate physiological or pathological LLPS.

Indexed as

Protein FoldingAnimalsHumansNeurodegenerative DiseasesProteostasis DeficienciesRNARNA-Binding ProteinsRNARNA-Binding Proteins

Identifiers

PMID34297914
PMCPMC8434763
OpenAlexW3183638587

What OpenQuestion 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 OpenQuestion graph.