Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Drosophila FMRP recruits the miRISC to target mRNAs to repress translation

Navneeta Kaul, Sarala J. Pradhan, Nathan G. Boin, Madeleine M. Mason, Julian Rosales, Emily L. Starke, Emily C. Wilkinson, View ORCID ProfileErich G. Chapman, View ORCID ProfileScott A. Barbee
doi: https://doi.org/10.1101/2023.05.03.539280
Navneeta Kaul
1Department of Biological Sciences, University of Denver, Denver, Colorado, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sarala J. Pradhan
1Department of Biological Sciences, University of Denver, Denver, Colorado, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathan G. Boin
1Department of Biological Sciences, University of Denver, Denver, Colorado, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Madeleine M. Mason
1Department of Biological Sciences, University of Denver, Denver, Colorado, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julian Rosales
2Department of Chemistry and Biochemistry, University of Denver, Denver, Colorado, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emily L. Starke
1Department of Biological Sciences, University of Denver, Denver, Colorado, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emily C. Wilkinson
1Department of Biological Sciences, University of Denver, Denver, Colorado, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erich G. Chapman
1Department of Biological Sciences, University of Denver, Denver, Colorado, USA
2Department of Chemistry and Biochemistry, University of Denver, Denver, Colorado, USA
3Molecular and Cellular Biophysics Program, University of Denver, Denver, Colorado, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Erich G. Chapman
Scott A. Barbee
1Department of Biological Sciences, University of Denver, Denver, Colorado, USA
3Molecular and Cellular Biophysics Program, University of Denver, Denver, Colorado, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Scott A. Barbee
  • For correspondence: scott.barbee@du.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and is caused by mutations in the gene encoding for the Fragile X messenger ribonucleoprotein (FMRP). FMRP is an evolutionarily conserved and neuronally enriched RNA binding protein (RBP) with functions in the control of processes including RNA editing, RNA transport, and protein translation. Specific target RNAs play critical roles in neurodevelopment including the regulation of neurite morphogenesis, synaptic plasticity, and cognitive function. The different biological functions of FMRP are modulated by its cooperative interaction with distinct sets of neuronal RNA and protein binding partners. Here, we focus on interactions between FMRP and components of the microRNA (miRNA) pathway. Using the Drosophila model system, we show that dFMRP can repress the translation of a reporter mRNA via a deadenylation-independent mechanism. This repression requires the activity of both AGO1 and GW182, conserved components of the miRNA-containing RISC (miRISC). Interestingly, we find that dFMRP can bind directly to a short stem loop structure in the reporter and that dFMRP binding is a prerequisite for repression by miR-958. Finally, we show that dFmr1 interacts genetically with GW182 to control neurite morphogenesis. Collectively, these data suggest the dFMRP can directly recruit the miRISC to nearby miRNA binding sites and then repress translation via the activity of the miRISC effector, GW182.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted May 03, 2023.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Drosophila FMRP recruits the miRISC to target mRNAs to repress translation
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Drosophila FMRP recruits the miRISC to target mRNAs to repress translation
Navneeta Kaul, Sarala J. Pradhan, Nathan G. Boin, Madeleine M. Mason, Julian Rosales, Emily L. Starke, Emily C. Wilkinson, Erich G. Chapman, Scott A. Barbee
bioRxiv 2023.05.03.539280; doi: https://doi.org/10.1101/2023.05.03.539280
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Drosophila FMRP recruits the miRISC to target mRNAs to repress translation
Navneeta Kaul, Sarala J. Pradhan, Nathan G. Boin, Madeleine M. Mason, Julian Rosales, Emily L. Starke, Emily C. Wilkinson, Erich G. Chapman, Scott A. Barbee
bioRxiv 2023.05.03.539280; doi: https://doi.org/10.1101/2023.05.03.539280

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Molecular Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4378)
  • Biochemistry (9570)
  • Bioengineering (7082)
  • Bioinformatics (24819)
  • Biophysics (12595)
  • Cancer Biology (9943)
  • Cell Biology (14332)
  • Clinical Trials (138)
  • Developmental Biology (7942)
  • Ecology (12091)
  • Epidemiology (2067)
  • Evolutionary Biology (15977)
  • Genetics (10913)
  • Genomics (14724)
  • Immunology (9859)
  • Microbiology (23616)
  • Molecular Biology (9471)
  • Neuroscience (50812)
  • Paleontology (369)
  • Pathology (1538)
  • Pharmacology and Toxicology (2677)
  • Physiology (4005)
  • Plant Biology (8651)
  • Scientific Communication and Education (1508)
  • Synthetic Biology (2388)
  • Systems Biology (6420)
  • Zoology (1345)