Control of noncoding RNA production and histone levels by a 5' tRNA fragment.
Small RNAs derived from mature tRNAs, referred to as tRNA fragments or "tRFs," are an emerging class of regulatory RNAs with poorly understood functions. We recently identified a role for one specific tRF-5' tRF-Gly-GCC, or tRF-GG-as a repressor 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-snoRNAs, scaRNAs, and snRNAs-that are dependent on Cajal bodies for stability and activity. Among these noncoding RNAs, regulation of the U7 snRNA by tRF-GG 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, on activity of a histone 3' UTR reporter, and ultimately on MERVL regulation could all be suppressed by manipulating U7 RNA levels. We additionally show that the related RNA-binding proteins hnRNPF and hnRNPH bind directly to tRF-GG, and are required for Cajal body biogenesis, positioning these proteins as strong candidates for effectors of tRF-GG function in vivo. Together, our data reveal a conserved mechanism for 5' tRNA fragment control of noncoding RNA biogenesis and, consequently, global chromatin organization.
['Boskovic|Ana|A|', 'Bing|Xin Yang|XY|', 'Kaymak|Ebru|E|', 'Rando|Oliver J|OJ|']
D000818:Animals D002460:Cell Line D020541:Coiled Bodies D005786:Gene Expression Regulation D006657:Histones D000066449:Human Embryonic Stem Cells D006801:Humans D051379:Mice D011485:Protein Binding D012342:RNA, Small Nuclear D012343:RNA, Transfer D022661:RNA, Untranslated D018626:Retroelements
histones tRNA fragment epigenetics