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Control of noncoding RNA production and histone levels by a 5' tRNA fragment.

Genes & development (2019-12-14)
Ana Boskovic, Xin Yang Bing, Ebru Kaymak, Oliver J Rando
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Histone H4 Antibody, pan, clone 62-141-13, rabbit monoclonal, clone 62-141-13, Upstate®, from rabbit
Sigma-Aldrich
Anti-Histone H3 Antibody, CT, pan, serum, Upstate®