Slicing tRNAs to boost functional ncRNA diversity

Abstract

Post-transcriptional cleavage of RNA molecules to generate smaller fragments is a widespread mechanism that enlarges the structural and functional complexity of cellular RNomes. Substrates for such RNA fragmentations are coding as well as non-protein-coding RNAs. In particular, fragments derived from both precursor and mature tRNAs represent one of the rapidly growing classes of post-transcriptional RNA pieces. Importantly, these tRNA fragments possess distinct expression patterns, abundance, cellular localizations, or biological roles compared with their parental tRNA molecules. Here we review recent reports on tRNA cleavage and attempt to categorize tRNA pieces according to their origin and cellular function. The biological scope of tRNA-derived fragments ranges from translation control, over RNA silencing, to regulating apoptosis, and thus clearly enlarges the functional repertoire of ncRNA biology.

Keywords: RNA fragmentation; RNA processing; RNA silencing; non-coding RNA; tRNA halves; tRNA-derived fragments; translation regulation.

Figure 1. Processing and function of tRNA pieces. Precursor tRNA (pre-tRNA) transcripts are processed by RNase P, RNase Z, and the splicing endonuclease to remove the 5′ leader, 3′ trailer, and (if present) intronic sequences (gray), respectively. If the 3′ CCA end is not encoded, the CCA-adding enzyme finally generates the crucial 3′ end, thus resulting in mature tRNAs. Both pre-tRNA and mature tRNAs can give rise to smaller tRNA pieces. Depending on their origin, they are referred to as 5′ leader-exon tRF, 3′ U tRF, 5′ tRF, 3′ CCA tRF, or as 5′ and 3′ tRNA halves (red). Diverse nucleases identified or suggested to be involved in tRNA maturation and tRNA fragmentation are listed in blue. Whereas the endonucleases involved in tRNA halves production are well studied (PrrC, colicin D, and colicin E5 in bacteria; Rny1 and γ-toxin in certain yeast strains; angiogenin in human), the processing enzymes involved in tRF generation are less clear (indicated by dashed arrows and question marks). Potential cellular targets of the individual tRNA fragment classes are indicated (purple box) and the suggested functions are given (yellow box). Functional evidence for some tRNA pieces is less clear and this is indicated by dashed lines. References for the functional implications of tRNA-derived pieces are listed at the bottom.

Figure 2. Distribution of tRNA pieces among the three domains of life. A Venn diagram illustrates the verified presence of the various tRNA-derived RNA pieces in prokaryotes (bacteria and archaea) and eukaryotes. Note that the absence of a particular tRNA fragment species in one of the domains does not necessarily imply its absence rather than it reflects our current experimental insight.