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Asp-GTC-3'tDR is an ischemia-induced tRNA-derived small RNA (tsRNA or tDR) derived from the 3' end of tRNA-Asp-GTC. It serves as an endogenous regulatory molecule that mitigates cardiac fibrosis and heart failure progression. Mechanistically, Asp-GTC-3'tDR enhances autophagic flux and suppresses TGFβ signaling and extracellular matrix assembly pathways. It interacts with ribosomal proteins and stalled ribosomes to promote the formation of stress granules, which are subsequently targeted for degradation via the autophagy pathway. Therapeutic delivery of Asp-GTC-3'tDR mimics using polymer nanoparticles has demonstrated the ability to alleviate adverse cardiac remodeling and improve cardiac function in preclinical models of myocardial infarction.
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