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tRNA-derived fragments (tRFs) are a class of small non-coding RNAs, typically 14 to 32 nucleotides in length, generated by the precise enzymatic cleavage of precursor or mature transfer RNAs [1]. They are categorized into distinct types—such as 5'-tRFs, 3'-tRFs, and tRNA halves (tiRNAs)—based on their cleavage site and origin within the tRNA molecule [2]. Far from being random degradation products, tRFs function as potent regulators of cellular homeostasis by modulating gene expression at the post-transcriptional level [3]. They achieve this by mimicking microRNAs to silence target mRNAs, inhibiting translation initiation, or sequestering RNA-binding proteins [4]. In various diseases, particularly cancer and neurodegenerative disorders, tRF expression profiles are significantly altered, contributing to tumor progression, metastasis, and cellular stress responses [5]. Consequently, tRFs are being investigated as promising diagnostic biomarkers due to their high stability in circulation and as therapeutic targets for oligonucleotide-based drugs [6]. Current therapeutic approaches involve using antisense oligonucleotides to inhibit pathological tRFs or synthetic mimics to restore the function of depleted tumor-suppressive fragments [6].
Regulation of gene expression through mRNA degradation, translational repression, or displacement of RNA-binding proteins from their targets.
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