tRNA-derived fragments (tRFs): establishing their turf in post-transcriptional gene regulation

Cell Mol Life Sci. 2021 Mar;78(6):2607-2619. doi: 10.1007/s00018-020-03720-7. Epub 2021 Jan 2.


Transfer RNA (tRNA)-derived fragments (tRFs) are an emerging class of conserved small non-coding RNAs that play important roles in post-transcriptional gene regulation. High-throughput sequencing of multiple biological samples have identified heterogeneous species of tRFs with distinct functionalities. These small RNAs have garnered a lot of scientific attention due to their ubiquitous expression and versatility in regulating various biological processes. In this review, we highlight our current understanding of tRF biogenesis and their regulatory functions. We summarize the diverse modes of biogenesis through which tRFs are generated and discuss the mechanism through which different tRF species regulate gene expression and the biological implications. Finally, we conceptualize research areas that require focus to strengthen our understanding of the biogenesis and function of tRFs.

Keywords: Non-coding RNAs; Post-transcriptional regulation; Small RNAs; tRFs; tRNA-derived fragments; tsRNA.

Publication types

  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Humans
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Plants / genetics
  • Plants / metabolism
  • RNA Processing, Post-Transcriptional
  • RNA, Small Untranslated / genetics
  • RNA, Small Untranslated / metabolism*
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism*
  • Ribonucleoproteins / metabolism


  • RNA, Small Untranslated
  • Ribonucleoproteins
  • RNA, Transfer