Abstract

The fragments that derive from transfer RNAs (tRNAs) are an emerging category of regulatory RNAs. Known as tRFs, these fragments were reported for the first time only a decade ago, making them a relatively recent addition to the ever-expanding pantheon of non-coding RNAs. tRFs are short, 16–35 nucleotides (nts) in length, and produced through cleavage of mature and precursor tRNAs at various positions. Both cleavage positions and relative tRF abundance depend strongly on context, including the tissue type, tissue state, and disease, as well as the sex, population of origin, and race/ethnicity of an individual. These dependencies increase the urgency to understand the regulatory roles of tRFs. Such efforts are gaining momentum, and comprise experimental and computational approaches. System-level studies across many tissues and thousands of samples have produced strong evidence that tRFs have important and multi-faceted roles. Here, we review the relevant literature on tRF biology in higher organisms, single cell eukaryotes, and prokaryotes.

Highlights

  • By all accounts, generation sequencing (NGS) has led to important discoveries while enabling many practical applications in biology and medicine

  • We focus on the short RNAs that are produced from transfer RNAs (tRNAs) and are known as tRNA-derived fragments [1,2]

  • Polacek and colleagues described the function of a 3 tRNA half from tRNAThr in T. brucei that post-transcriptionally regulates translation via ribosome interactions [71]. These authors note that T. brucei lacks Angiogenin and Rny1p homologues, and that the observed tRNA halves do not depend on Dicer, further emphasizing that currently unknown proteins are linked to tRNA-derived fragments (tRFs) biogenesis

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Summary

Introduction

Generation sequencing (NGS) has led to important discoveries while enabling many practical applications in biology and medicine. Hormone signaling was shown to induce angiogenin-mediated tRNA cleavage in human prostate and breast tumor cell lines [28]. The recent finding that only some tRNA halves depend on Angiogenin [27] suggests the existence of yet-to-be-defined cleavage mechanisms.

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