Transfer RNA-derived fragments target and regulate ribosome-associated aminoacyl-transfer RNA synthetases

Abstract

Ribosome-associated noncoding (ranc) RNAs are a novel class of short regulatory RNAs with functions and origins that have not been well studied. In this present study, we functionally characterized the molecular activity of Saccharomyces cerevisiae transfer RNA (tRNA)-derived fragments (tRFs) during protein biosynthesis. Our results indicate ribosome-associated tRFs derived from both 5' (ranc-5'-tRFs) and 3'-part of tRNAs (ranc-3'-tRFs) have regulatory roles during translation. We demonstrated five 3'-tRFs and one 5'-tRF associate with a small ribosomal subunit and aminoacyl-tRNA synthetases (aa-RSs) in yeast. Furthermore, we discovered that four yeast aa-RSs interact directly with yeast ribosomes. tRFs interactions with ribosome-associated aa-RSs correlate with impaired efficiency of tRNA aminoacylation.

Arabidopsis tRNA-derived fragments as potential modulators of translation

“…This may suggest the existence of a still unknown but conserved process of global translation regulation by tRFs between animals and plants, and future work is required to verify this hypothesis. This is different to what has been described in the archaea Haloferax volcanii where s-tRFs inhibit translation by binding the small ribosomal subunit and competing with mRNA association [22] or in Saccharomyces cerevisiae where l-tRFs negatively affect protein synthesis by interacting with aminoacyl-tRNA synthetases and the small ribosomal subunit [37]. Finally, in Trypanosoma brucei, a l-tRF deriving from a tRNA Thr induced under nutrient starvation has an opposite effect, which is to stimulate translation by binding to ribosomes and polysomes [23].…”

Transfer RNA-Derived Small RNAs: Another Layer of Gene Regulation and Novel Targets for Disease Therapeutics

“…104 tsRNAs were also shown to interact with ribosome-associated aminoacyl-tRNA synthetases in yeast and inhibited in vitro translation through effects on tRNA aminoacylation. 105 Recently, ribosome-associated translation stimulation was also reported. Fricker et al 106 analyzed the small non-coding RNA interactome of ribosomes in Trypanosoma brucei during different growth conditions and life stages and found that Thr3 0 tRNA half (tRNA Thr 3 0 half) was markedly induced under nutrient deprivation.…”

Multiple ribonuclease A family members cleave transfer RNAs in response to stress

“…In this study, we tested whether ANG cleaves the 3'-CCA termini of tRNAs in vivo. If ANG efficiently cleaves 3'-CCA termini in vivo, it could contribute to stress-induced translational repression by mechanisms distinct from the reported before, where tRNA fragments directly interact with translational machinery (13,(48)(49)(50)(51)(52). However, our data using RNA-seq reveal that ANG does not affect the percentage of CCA-or CC-terminating species in tRNA fractions, thus demonstrating that ANG does not efficiently cleave 3'-CCA termini in vivo (Fig.…”