Small RNAs derived from mature tRNAs, referred to as tRNA fragments or tRFs, are an emerging class of regulatory RNAs with poorly understood functions in cellular regulation. We recently identified a role for one specific tRF  5 tRF-Gly-GCC, or tRF-GG  in repression of genes associated with the endogenous retroelement MERVL, but the mechanistic basis for this regulation was unknown. Here, we show that tRF-GG plays a role in production of a wide variety of noncoding RNAs normally synthesized in Cajal bodies. Among these noncoding RNAs, tRF-GG regulation of the U7 snRNA modulates heterochromatin-mediated transcriptional repression of MERVL elements by supporting an adequate supply of histone proteins. Importantly, the effects of inhibiting tRF-GG on histone mRNA levels, activity of a histone 3 UTR reporter, and ultimately on MERVL regulation could all be suppressed by the U7 RNA. We show that the related RNA-binding proteins hnRNPF and H bind directly to tRF-GG, and are required for Cajal body biogenesis. Together, our data reveal a conserved mechanism for 5 tRNA fragment control of noncoding RNA biogenesis and, consequently, in global chromatin organization. SOURCE: Oliver Rando (oliver.rando@umassmed.edu) -  UMass Medical School

Pluto Bioinformatics

GSE127247 (mouse): Control of noncoding RNA production and histone levels by a 5 tRNA fragment