tRF

tRNA-derived fragments, or tRFs, are a class of small non-coding RNAs generated from transfer RNAs. They are typically 14 to 28 nucleotides long, though longer tRNA halves can arise under stress. tRFs are produced by precise cleavage of mature tRNAs or precursor tRNA transcripts and have been identified in a wide range of organisms, including bacteria, archaea, and eukaryotes.

tRFs are commonly categorized by their origin within the tRNA molecule. tRF-5s come from the 5' end of mature tRNA, tRF-3s come from the 3' end of mature tRNA, and tRF-1s originate from the 3' trailer of precursor tRNA. Internal tRFs, or i-tRFs, are generated from internal regions of mature tRNA. In response to cellular stress, tRNAs can be cleaved in the anticodon loop by nucleases such as angiogenin to produce tRNA halves, also known as tiRNAs, which include 5'-tiRNA and 3'-tiRNA forms.

Biogenesis of tRFs involves multiple nucleases and pathways, and can be dependent or independent of Dicer, depending on the particular fragment and organism. The functional repertoire of tRFs is diverse and context-dependent. Some tRFs associate with Argonaute proteins and participate in post-transcriptional gene regulation, similar in some respects to microRNAs, while others influence translation initiation or elongation, modulate ribosome or tRNA biogenesis, or participate in stress granule dynamics.

tRFs are studied for their roles in development, cancer, aging, and neurological disorders, and are explored as potential biomarkers in body fluids and as therapeutic targets. They are cataloged in public resources such as tRFdb and MINTbase, which collect sequence, origin, and expression data across species.