Human tRNA-derived small RNAs in the global regulation of RNA silencing

Department of Pediatrics, Stanford University, Stanford, California 94305, USA.
RNA (Impact Factor: 4.94). 02/2010; 16(4):673-95. DOI: 10.1261/rna.2000810
Source: PubMed


Competition between mammalian RNAi-related gene silencing pathways is well documented. It is therefore important to identify all classes of small RNAs to determine their relationship with RNAi and how they affect each other functionally. Here, we identify two types of 5'-phosphate, 3'-hydroxylated human tRNA-derived small RNAs (tsRNAs). tsRNAs differ from microRNAs in being essentially restricted to the cytoplasm and in associating with Argonaute proteins, but not MOV10. The first type belongs to a previously predicted Dicer-dependent class of small RNAs that we find can modestly down-regulate target genes in trans. The 5' end of type II tsRNA was generated by RNaseZ cleavage downstream from a tRNA gene, while the 3' end resulted from transcription termination by RNA polymerase III. Consistent with their preferential association with the nonslicing Argonautes 3 and 4, canonical gene silencing activity was not observed for type II tsRNAs. The addition, however, of an oligonucleotide that was sense to the reporter gene, but antisense to an overexpressed version of the type II tsRNA, triggered robust, >80% gene silencing. This correlated with the redirection of the thus reconstituted fully duplexed double-stranded RNA into Argonaute 2, whereas Argonautes 3 and 4 were skewed toward less structured small RNAs, particularly single-strand RNAs. We observed that the modulation of tsRNA levels had minor effects on the abundance of microRNAs, but more pronounced changes in the silencing activities of both microRNAs and siRNAs. These findings support that tsRNAs are involved in the global control of small RNA silencing through differential Argonaute association, suggesting that small RNA-mediated gene regulation may be even more finely regulated than previously realized.

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Available from: Mark A Kay, Jun 28, 2014
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    • "The largest proportion of tRF5s was between 30 and 34 nucleotides in length , with tRF5s of 31 and 34 nucleotides being the most prevalent . Previous studies indicated that length of tRF5s was between 18 and 25 nucleotides ( Lee et al . , 2009 ) or between 21 and 22 nucleotides ( Haussecker et al . , 2010 ) . Wang et al . ( 2013 ) , identified a 31 nucleotide tRF5 ( tRF5 - Glu ) as being a suppressor in messenger RNA in cytoplasm in the presence of bovine respiratory syncytial virus . It is unknown if differences in"
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    Frontiers in Genetics 08/2015; 6:271. DOI:10.3389/fgene.2015.00271
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    • "In work published in 2013 (Galizi et al. 2013), we described a new phenomenon occurring in T. gondii and Plasmodium berghei consisting on production of halftRNAs in response to several stimuli, such as starvation, and during parasite differentiation. Although we have not investigated the role of these molecules in parasites, halftRNAs in other organisms have been shown to bind target messengers and drive cleavage of these transcripts by tRNaseZ (Haussecker et al. 2010). We have identified two putative tRNaseZs in both T. gondii and Plasmodium species (Galizi et al. 2013) and hypothesized that these proteins may work in concert with half-tRNAs to regulate gene expression. "
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