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

Using an elegant biochemical approach, named HITS-ABt (hIgh-throughput sequencing of RNAs associated with biotinylated tRF), to capture tRF5-GluCTC-containing ribonucleoprotein complexes combined with bioinformatics analysis, we have identified a number of potential cellular mRNA targets of tRF5-GluCTC. One of the candidate mRNAs was shown to be a direct target of tRF5-GluCTC. Mechanistically, tRF5-GluCTC recognizes a target site in the 3ËŠ-untranslated region of APOER2 mRNA and suppresses its expression by an unknown mechanism. Further analysis identified a previously unappreciated role for APOER2 protein in antiviral defense against RSV infection [61] . Thus, we have illuminated the roles of tRFs in host-virus interactions and described a novel molecular mechanism for host response regulation via gene targeting at posttranscriptional level, proving a potential therapeutic target to control RSV replication by regulating tRFs induction. As another example of tRFs with a positive effect on viral replication, a tRF-3 derived from tRNA Pro (tRF-3019) has been suggested to function as a primer for reverse transcrip-tion of human T-cell leukemia virus-1 [62] .