tRNA-Derived Fragments (tRFs): Emerging New Roles for an Ancient RNA in the Regulation of Gene Expression

Abstract

This review will summarise the recent discoveries and current state of research on short noncoding RNAs derived from tRNAs-known as tRNA-derived fragments (tRFs). It will describe the features of the known subtypes of these RNAs; including sequence characteristics, protein interactors, expression characteristics, biogenesis, and similarity to canonical miRNA pathways. Also their role in regulating gene expression; including mediating translational suppression, will be discussed. We also highlight their potential use as biomarkers, functions in gene regulation and links to disease. Finally, this review will speculate as to the origin and rationale for the conservation of this novel class of noncoding RNAs amongst both prokaryotes and eukaryotes.

Keywords: gene regulation; small RNA; tRF; tRNA; tRNA-derived fragments.

Figure 1

tRNA biogenesis, types of tRFs, nucleases involved in their biogenesis, and examples of their functions. Outline of mature tRNA biogenesis (dark grey) from pol(III)-transcribed pre-tRNA precursors which undergo nuclease cleavage by RNase P and RNase Z, enzymatic modification including addition of CCA trinucleotide and folding into mature tRNA. Four recognised types of tRFs and their identified nucleases (if any) shown including (A) 5′ tRF; (B) 3′ CCA tRF; (C) 3′ U tRF; (D) itRF. Examples of functions for tRFs in the literature (light grey) including: (1) gene repression of mRNAs via 3′UTR targeting [9,10] and reporter construct silencing [11]; (2) targeting of ribosomes and inhibition of translation [12,13]; (3) modulators of cell proliferation [14]; (4) promotion of Xrn2-mediated exonuclease degradation of mRNAs [15]; (5) displacement of Ybx1 protein from mRNA and promotion of degradation [16]; (6) sense-induced trans-silencing [17].