Novel insights into the emerging roles of tRNA-derived fragments in mammalian development

tRNA-derived fragments or tRFs were long considered merely degradation intermediates of full-length tRNAs; however, emerging research is highlighting unanticipated new and highly distinct functions in epigenetic control, metabolism, immune activity and stem cell fate commitment. Importantly, recent studies suggest that RNA epitranscriptomic modifications may provide an additional regulatory layer that dynamically directs tRF activity in stem and cancer cells. In this review, we explore current work illustrating unanticipated roles of tRFs in mammalian stem cells with a focus on the impact of post-transcriptional RNA modifications for the biogenesis and function of this growing class of small noncoding RNAs.