Evidence map›Paper›PMID 37696852›Full record

ArticleNature communications2023

Single-molecule imaging reveals distinct elongation and frameshifting dynamics between frames of expanded RNA repeats in C9ORF72-ALS/FTD.

Malgorzata J Latallo, Shaopeng Wang, Daoyuan Dong, Blake Nelson, Nathan M Livingston, Rong Wu, Ning Zhao, Timothy J Stasevich, Michael C Bassik, Shuying Sun and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Article
  3. RAN Translation-Coupled Decay of theInternational journal of molecular sciences · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Quality control and signaling pathways at stalled ribosomes.Experimental & molecular medicine · 2026
    Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. 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

11 authors at 3 institutions in 1 country.

Malgorzata J Latallo *Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Shaopeng Wang *Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Daoyuan Dong *Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Blake NelsonDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.ORCID http://orcid.org/0000-0002-0678-1501
Nathan M LivingstonDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.ORCID http://orcid.org/0000-0003-4670-708X
Rong WuDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Ning ZhaoDepartment of Biochemistry and Molecular Genetics, University of Colorado-Anschutz Medical Campus, Aurora, CO, 80045, USA.
Timothy J StasevichDepartment of Biochemistry and Molecular Genetics, University of Colorado-Anschutz Medical Campus, Aurora, CO, 80045, USA.ORCID http://orcid.org/0000-0002-0151-6274
Michael C BassikDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0001-5185-8427
Shuying SunCenter for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. shuying.sun@jhmi.edu.ORCID http://orcid.org/0000-0002-8449-7370
Bin WuDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. bwu20@jhmi.edu.ORCID http://orcid.org/0000-0002-9442-3041
Johns Hopkins University · USUniversity of Colorado Anschutz Medical Campus · USStanford University · US

Funding

BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
PROGRAM IN MOLECULAR BIOPHYSICST32GM008403 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI BARRICK, DOUGLAS E. · 1990 to 2019
$13.5M
Single molecule study of C9ORF72 repeat RNA metabolisms in ALS/FTDRF1NS113820 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SUN, SHUYING, WU, BIN · 2020 to 2025
$6.2M
Program of Molecular BiophysicsT32GM135131 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Karen G. Fleming · 2020 to 2026
$5.4M
The role of m6A RNA methylation in C9ORF72-ALS/FTDRF1NS127925 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SUN, SHUYING · 2022 to 2024
$2.0M
Molecular mechanism of dipeptide repeat protein production from hexanucleotide repeats in C9ORF72-related ALS and FTDR01NS107347 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SUN, SHUYING · 2018 to 2022
$1.8M
Developing optogenetic and chemogenetic approaches to control RNA metabolism in live cellsR01GM136897 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI WU, BIN · 2021 to 2024
$1.8M
Dysregulation of inhibitory synapse by poly-GR in C9ORF72-ALS/FTDR21AG072078 · NIA · JOHNS HOPKINS UNIVERSITY · PI SUN, SHUYING · 2021 to 2021
$450k
NIA NIH HHS R21 AG072078NIGMS NIH HHS R01 GM136897NIGMS NIH HHS T32 GM007445NIGMS NIH HHS T32 GM008403NIGMS NIH HHS T32 GM135131NINDS NIH HHS R01 NS107347NINDS NIH HHS RF1 NS113820NINDS NIH HHS RF1 NS127925
6 · The paper itself

Abstract

C9ORF72 hexanucleotide repeat expansion is the most common genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). One pathogenic mechanism is the accumulation of toxic dipeptide repeat (DPR) proteins like poly-GA, GP and GR, produced by the noncanonical translation of the expanded RNA repeats. However, how different DPRs are synthesized remains elusive. Here, we use single-molecule imaging techniques to directly measure the translation dynamics of different DPRs. Besides initiation, translation elongation rates vary drastically between different frames, with GP slower than GA and GR the slowest. We directly visualize frameshift events using a two-color single-molecule translation assay. The repeat expansion enhances frameshifting, but the overall frequency is low. There is a higher chance of GR-to-GA shift than in the reversed direction. Finally, the ribosome-associated protein quality control (RQC) factors ZNF598 and Pelota modulate the translation dynamics, and the repeat RNA sequence is important for invoking the RQC pathway. This study reveals that multiple translation steps modulate the final DPR production. Understanding repeat RNA translation is critically important to decipher the DPR-mediated pathogenesis and identify potential therapeutic targets in C9ORF72-ALS/FTD.

Indexed as

Amyotrophic Lateral SclerosisFrontotemporal DementiaC9orf72 ProteinCarrier ProteinsDipeptidesHumansRNASingle Molecule ImagingC9orf72 ProteinCarrier ProteinsDipeptidesRNAZNF598 protein, human

Identifiers

PMID37696852
PMCPMC10495369
OpenAlexW4386594437

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.