Evidence map›Paper›PMID 37791873›Full record

ArticleNucleic acids research2023

Drosha-dependent microRNAs modulate FUS-mediated neurodegeneration in vivo.

Sukhleen Kour, Tyler Fortuna, Eric N Anderson, Darilang Mawrie, Jessica Bilstein, Ramakrishnan Sivasubramanian, Caroline Ward, Rishit Roy, Dhivyaa Rajasundaram, Jared Sterneckert and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. IsomiR Utility in Amyotrophic Lateral Sclerosis Prognostication.medRxiv : the preprint server for health sciences · 2025
    Article
  4. Article
  5. Review
  6. Regulation of the microprocessor by post-translational modifications.Frontiers in cell and developmental biology · 2025
    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 2 countries.

Sukhleen KourDepartment of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA.
Tyler FortunaDepartment of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA.
Eric N AndersonDepartment of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA.
Darilang MawrieDepartment of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA.
Jessica BilsteinCenter for Regenerative Therapies TU Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, 01307, Germany.
Ramakrishnan SivasubramanianCenter for Regenerative Therapies TU Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, 01307, Germany.
Caroline WardDepartment of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA.
Rishit RoyDepartment of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA.
Dhivyaa RajasundaramDepartment of Pediatrics, Division of Health Informatics, Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.
Jared SterneckertCenter for Regenerative Therapies TU Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, 01307, Germany.
Udai Bhan PandeyDepartment of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA.ORCID 0000-0002-6267-0179
Children's Hospital of Pittsburgh · USTechnische Universität Dresden · DEUniversity Hospital Carl Gustav Carus · DE

Funding

Cellular and Molecular Mechanisms of FUS-related Amyotrophic Lateral SclerosisR01NS081303 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PANDEY, UDAI B · 2013 to 2023
$3.6M
High-Throughput Computing for Genomics and Bioinformatics ResearchS10OD028483 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEE, ADRIAN V · 2021 to 2021
$574k
NIH HHS S10 OD028483NINDS NIH HHS R01 NS081303
6 · The paper itself

Abstract

Mutations in the Fused in Sarcoma (FUS) gene cause the familial and progressive form of amyotrophic lateral sclerosis (ALS). FUS is a nuclear RNA-binding protein involved in RNA processing and the biogenesis of a specific set of microRNAs. Here we report that Drosha and two previously uncharacterized Drosha-dependent miRNAs are strong modulators of FUS expression and prevent the cytoplasmic segregation of insoluble mutant FUS in vivo. We demonstrate that depletion of Drosha mitigates FUS-mediated degeneration, survival and motor defects in Drosophila. Mutant FUS strongly interacts with Drosha and causes its cytoplasmic mis-localization into the insoluble FUS inclusions. Reduction in Drosha levels increases the solubility of mutant FUS. Interestingly, we found two Drosha dependent microRNAs, miR-378i and miR-6832-5p, which differentially regulate the expression, solubility and cytoplasmic aggregation of mutant FUS in iPSC neurons and mammalian cells. More importantly, we report different modes of action of these miRNAs against mutant FUS. Whereas miR-378i may regulate mutant FUS inclusions by preventing G3BP-mediated stress granule formation, miR-6832-5p may affect FUS expression via other proteins or pathways. Overall, our research reveals a possible association between ALS-linked FUS mutations and the Drosha-dependent miRNA regulatory circuit, as well as a useful perspective on potential ALS treatment via microRNAs.

Indexed as

Drosophila ProteinsHeterogeneous-Nuclear Ribonucleoprotein Group F-HMicroRNAsRibonuclease IIIAmyotrophic Lateral SclerosisAnimalsDrosophilaHumansMutationNeurodegenerative DiseasesNeuronsRNA-Binding Proteinsdrosha protein, DrosophilaDrosophila ProteinsFUS protein, DrosophilaHeterogeneous-Nuclear Ribonucleoprotein Group F-HMicroRNAsRibonuclease IIIRNA-Binding Proteins

Identifiers

PMID37791873
PMCPMC10639082
OpenAlexW4387326796

What OpenQuestion 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 OpenQuestion graph.