Transfer RNA‐derived fragments: origins, processing, and functions

Abstract

Deep sequencing approaches have revealed multiple types of small RNAs with known and unknown functions. In this review we focus on recently identified group of small RNAs that are derived from tRNAs, tRNA fragments (tRFs). We review the mechanism of their processing and their functions in mammalian cells, and highlight points of possible cross-talk between tRFs and the canonical small RNA pathway characterized by siRNAs, miRNAs and piRNAs. We also propose a nomenclature that is based on their processing characteristics.

Circulating microRNA signature of genotype‐by‐age interactions in the long‐lived Ames dwarf mouse

“…Recently, deep sequencing unraveled that tRNA, rRNA, snoRNA, and YRNA can undergo processing into smaller RNA molecules (Rutjes et al ., 1999; Rother & Meister, 2011; Sobala & Hutvagner, 2011). These new small RNAs are being noticed only now because most studies focused on sequencing reads derived from miRNAs.…”

“…More recently, deep sequencing technologies allowed the identification of new types of small RNAs derived from the processing of already known sncRNAs including tRNA (Rutjes et al ., 1999; Rother & Meister, 2011; Sobala & Hutvagner, 2011). There is evidence implicating these derivatives of sncRNAs in cell‐to‐cell communication both in normal biology and in disease states (Cortez et al ., 2011; Hoy & Buck, 2012; Shah & Calin, 2012; Turchinovich et al ., 2012; Kosaka et al ., 2013).…”

“…Our deep sequencing studies of serum/plasma have consistently detected tRNA‐derived RNAs of size 30–33 nt (Dhahbi et al ., 2013a,b). Intracellular tRNA‐derived small RNAs are classified into two types based on their size (Sobala & Hutvagner, 2011; Martens‐Uzunova et al ., 2013): tRNA halves with size of 30–40 nt produced by cleavage of mature tRNAs, and shorter tRNA‐derived fragments (tRFs) of size 18–22 nt produced from both mature and pre‐tRNAs by Dicer or RNase Z (Thompson et al ., 2008; Cole et al ., 2009; Fu et al ., 2009; Lee et al ., 2009; Thompson & Parker, 2009a; Pederson, 2010; Sobala & Hutvagner, 2011). The tRNA halves class includes 5′‐ and 3′‐tRNA halves that were first observed in stressed cultured cells where they are produced by cleavage of tRNAs near or at the anticodon loop with the ribonuclease Rny1 in Saccharomyces cerevisiae (Thompson & Parker, 2009b) and Angiogenin in higher eukaryotes (Fu et al ., 2009; Yamasaki et al ., 2009).…”

Four-leaf clover qRT-PCR: A convenient method for selective quantification of mature tRNA

“…10,11 tRNAs have further been reported to serve as a source of small functional RNAs. [12][13][14] Numerous tRNA-interacting proteins have recently been proposed, 15 indicating the scope of tRNA biological functions may be far beyond that previously assumed.…”

A load of small RNAs in the sperm — how many bits of hereditary information?

“…tRNAs are abundant and functionally important noncoding RNAs with highly conserved and extensive posttranscriptional processing. Maturation of tRNA generates several byproduct species, including tRNA fragments derived from tRNA 3′-trailer processed by tRNase Z or tRNA 5′-leader by RNase P. A parallel has been drawn with a different set of RNAi machinery enzymes [7]. A functional difference independent of protein synthesis is suggested with a novel role in modulation of gene expression.…”