5tRF

5tRF, also referred to as a 5'-tRNA-derived fragment, is a class of small non-coding RNA fragments derived from the 5' end of transfer RNAs. These fragments are typically 14 to 30 nucleotides in length and originate from mature tRNA or its precursors, produced by cleavage at the 5' end of the molecule. They are distinguished from tRNA halves, or tiRNAs, which arise under stress and are generally longer.

Biogenesis of 5tRFs involves endonucleolytic processing by ribonucleases. In some systems, enzymes such as Dicer contribute to their generation, while in others RNases such as RNase Z or related nucleases are implicated. Their production can be constitutive or stress-induced, and tRNA sequence, structure, and modification patterns influence cleavage efficiency. 5tRFs have been detected across a range of organisms, including animals, plants, and some microbes, and can be found in extracellular fluids and vesicles, suggesting potential intercellular signaling roles.

Functions and significance of 5tRFs are still being defined and appear to be context dependent. In several models, 5tRFs participate in post-transcriptional regulation of gene expression, sometimes associating with Argonaute proteins and exhibiting microRNA-like activity by guiding target repression. They can influence translation initiation or mRNA stability and have been linked to cellular stress responses, development, viral infection, and cancer biology. The exact targets and mechanisms can vary by species and cellular context, and ongoing studies continue to refine their biological relevance and therapeutic potential.

Terminology can vary, with 5tRFs sometimes described as tRF-5s; together with 3'-tRFs and internal tRFs (i-tRFs), they comprise the broader class of tRNA-derived fragments (tsRNA).