tRF-AspGTC Promotes Intracranial Aneurysm Formation by Controlling TRIM29-Mediated Galectin-3 Ubiquitination

tRF-AspGTC Promotes Intracranial Aneurysm Formation by Controlling TRIM29-Mediated Galectin-3 Ubiquitination

Transfer RNA-derived small RNAs, a recently identified class of small noncoding RNAs, play a crucial role in regulating gene expression and are implicated in cerebrovascular diseases. However, the specific biological roles and mechanisms of transfer RNA-derived small RNAs in intracranial aneurysms (...

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Bibliographic Details
Main Authors: Chao Wang, Bing Yu, Han Zhou, Huanting Li, Shifang Li, Xiaolu Li, Wentao Wang, Yugong Feng, Tao Yu
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2025-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0574
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Summary:Transfer RNA-derived small RNAs, a recently identified class of small noncoding RNAs, play a crucial role in regulating gene expression and are implicated in cerebrovascular diseases. However, the specific biological roles and mechanisms of transfer RNA-derived small RNAs in intracranial aneurysms (IAs) remain unclear. In this study, we identified that the transfer RNA-Asp-GTC derived fragment (tRF-AspGTC) is highly expressed in the IA tissues of both humans and mice. tRF-AspGTC promotes IA formation by facilitating the phenotypic switching of vascular smooth muscle cells, increasing of matrix metalloproteinase 9 expression, and inducing of oxidative stress and inflammatory responses. Mechanistically, tRF-AspGTC binds to galectin-3, inhibiting tripartite motif 29-mediated ubiquitination and stabilizing galectin-3. This stabilization activates the toll-like receptor 4/MyD88/nuclear factor kappa B pathway, further driving phenotypic switching and inflammation. Clinically, circulating exosomal tRF-AspGTC demonstrates strong diagnostic efficacy for IAs and is identified as an independent risk factor for IA occurrence. These findings highlight the potential of tRF-AspGTC as a promising diagnostic biomarker and therapeutic target for IAs.
ISSN:2639-5274

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