Small Non-coding Transfer RNA-Derived RNA Fragments (tRFs): Their Biogenesis, Function and Implication in Human Diseases

Fu, Yu; Lee, Inhan; Lee, Yong Sun; Bao, Xiaoyong

It is now well known that mammalian genomes encode, in addition to protein-coding genes, RNA molecules that have no protein-coding capacity, and thus are referred to as non-coding RNAs (ncRNAs) [1] . Recent high throughput sequencing data suggest that there are about four times as many ncRNA transcripts as there are protein-coding RNA transcripts in human cells. While some ncRNAs, such as ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), and those well-studied ones including microRNAs (miRNAs) and small interfering RNAs (siRNAs), are recognized as functional molecules, the majority of ncRNAs and their biological roles in mammals are underappreciated, as evolution would have favored against such gratuitous and wasteful transcription [2] . However, accumulating evidence has exhibited a remarkable degree of their involvement in many biological events including cell proliferation, cellular stress responses, host immune responses and virus replication [3] [4] [5] [6] . Based on their size, ncRNAs are classified into long, medium, and small ones. Those longer than 200 nucleotides (nt) are termed as long (or large) ncRNAs (lncRNAs) and include the majority of nuclear ncRNAs. Those ranging 40−200 nt are medium-sized ncRNAs including many classic ncRNAs such as 5S rRNA, tRNAs, small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), etc. ncRNAs shorter than 40 nt are termed small ncRNAs (sncRNAs) that have been extensively studied in the last two decades and will be elaborated in the next section. In this review, we will focus on a recently discovered class of sncRNAs called tRNA-derived RNA fragments (tRFs), as data from several groups including those from us suggested them to be emerging functional molecules.