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 functionality of ncRNAs was initially bolstered by the discovery showing that sncRNAs are capable of mediating both transcriptional and post-transcriptional gene silencing [7] . The most extensively studied among them are miRNAs that regulate target mRNAs post-transcriptionally in animals and plants [8] [9] [10] . Another class of sncRNAs is siRNAs that are closely related to miRNAs [11] . Although naturally occurring siRNAs have been reported to be present in some mammals in addition to plants and flies [12, 13] , siRNAs are more renowned as an experimental tool in mammalian cells. The gene silencing by synthetic doublestranded RNAs (dsRNAs) and their Dicer-cleavage products (that are siRNAs) is called RNA interference (RNAi) and has been being used as a popular gene knockdown method [3] . This technical breakthrough was well recognized and celebrated by the 2006 Nobel Prize, which was awarded to the two scientists who discovered RNAi [14, 15] . A number of other sncRNAs have also been identified in various organisms [16, 17] , including piwi-interacting RNA (piRNA), repeat-associated siRNA (rasiRNA), tiny ncRNAs (tncRNA), heterochromatic small RNA (21U-RNA, hcRNA), scan RNA (scnRNA), transcription initiation RNA (tiRNA) [18] , and promoter/termini-associated sRNA (PASR/TASR) [19] . Although some of these have been shown to play roles in several biological processes such as heterochromatin formation and transposon silencing, their functions are largely unknown and detailed description of them is beyond the scope of this review [10] .