Transfer RNA-derived fragment (tRF)

Transfer RNA-derived fragments (tRFs) are a diverse class of small non-coding RNAs, typically 14–50 nucleotides in length, generated by the precise and regulated cleavage of precursor or mature transfer RNAs by ribonucleases such as Angiogenin or Dicer [4, 6]. Initially dismissed as random degradation byproducts, tRFs are now recognized as functional molecules that play critical roles in regulating cellular homeostasis, gene expression, and protein synthesis [8, 11]. They are classified into several distinct types—including tRF-1, tRF-3, tRF-5, and tRNA halves (tiRNAs)—based on their origin and specific cleavage sites [4, 12]. tRFs exert their biological effects through various mechanisms, such as acting in a microRNA-like manner to silence target mRNAs, displacing RNA-binding proteins like YBX1 to affect transcript stability, or directly inhibiting translation initiation [3, 12]. Their dysregulation is strongly associated with the pathogenesis of multiple diseases, most notably cancer, where they can function as either oncogenes or tumor suppressors depending on the cellular context [1, 4, 6]. In the therapeutic landscape, tRFs are being explored as both highly sensitive diagnostic biomarkers in liquid biopsies and as druggable targets, with experimental strategies focusing on antisense oligonucleotides for inhibition or synthetic mimics for functional restoration [2, 5, 7].

Other names

tRNA-derived small RNAtsRNAtRNA-derived stress-induced RNAtiRNAtRNA halves5'-tRF3'-tRFi-tRF1-tRF3'U-tRFSHOT-RNA

Modulation of target mRNA stability and translation through microRNA-like silencing, competitive displacement of RNA-binding proteins (e.g., YBX1), or direct interference with translation initiation complexes and ribosome biogenesis.