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TRIM25 dictates selective miRNA loading into extracellular vesicles during inflammation
Kayla E King1,2, Priyanka Ghosh1,2, Ann L Wozniak3,4
1Department of Internal Medicine, University of Kansas Medical Center, Mailstop 1018, Kansas City, KS, 66160, USA.
Scientific Reports
|December 22, 2023
Summary
Inflammation promotes the loading of RNA-binding protein FMR1 and microRNA miR-155 into extracellular vesicles (EVs). This process is controlled by the E3 ligase TRIM25, which ubiquitinates FMR1, impacting EV biogenesis.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Extracellular vesicles (EVs) mediate cell-to-cell communication via specific biomolecules.
- Understanding selective EV cargo loading is crucial for deciphering physiological and pathological roles.
Purpose of the Study:
- To identify novel mechanisms regulating inflammation-mediated cargo loading into EVs.
- To investigate the role of E3 ligase TRIM25 in the EV loading of FMR1 and miR-155.
Main Methods:
- Investigated the interaction between TRIM25, FMR1, and RILP.
- Utilized knockdown of TRIM25 to assess its effect on FMR1 and miR-155 EV loading.
- Analyzed K63-ubiquitination of FMR1.
Main Results:
- TRIM25 targets FMR1 for K63-ubiquitination, promoting its interaction with the EV loading machinery via RILP.
- TRIM25 knockdown disrupts FMR1-RILP interaction and prevents FMR1 and miR-155 loading into EVs.
- Demonstrated TRIM25's critical role in inflammation-mediated EV cargo selection.
Conclusions:
- TRIM25-mediated ubiquitination of FMR1 is essential for inflammation-induced EV loading of FMR1 and miR-155.
- Findings provide insights into EV biogenesis regulation and potential therapeutic targets.
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