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

The human genome encodes hundreds of tRNA genes and pseudogenes. In the past two decades, an increasing number of reports have revealed abundant expression of functional tRFs; thus, it now appears highly plausible that cells use tRNAs as a source for functional sncRNAs to modulate biological processes beyond its translation function. It is imperative to discriminate functional tRNA fragments from "meaningless" degradation products, and to biochemically elucidate the factors in their biogenesis as well as to determine their molecular functions. Although tRFs, at least the tRF-5s induced by RSV, regulate gene expression at post-transcriptional stages in the cytoplasm, the precise mechanism is yet to be clarified. Like miRNAs, tRFs can repress target mRNAs by inhibiting their translation or facilitating their decay. These questions can be answered by analyzing their localization, identifying their interacting protein partners besides Argonaute proteins, and examining various biological phenomena in response to the changes in the expression of tRFs. Bioinformatics studies with the support from biochemical assays have identified numerous novel tRNA-interacting proteins [68] , implying that the biological functions of tRNAs and their fragments may be way beyond our expectations. Further combination of computational and biochemical efforts will significantly advance our understanding of functional tRFs and expand our knowledge regarding the tRNA world.