Ameres, S. L. et al. Target RNA-directed trimming and tailing of small silencing RNAs. Science 328, 1534-1539

Howard Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Science (Impact Factor: 33.61). 06/2010; 328(5985):1534-9. DOI: 10.1126/science.1187058
Source: PubMed


In Drosophila, microRNAs (miRNAs) typically guide Argonaute1 to repress messenger RNA (mRNA), whereas small interfering RNAs (siRNAs) guide Argonaute2 to destroy viral and transposon RNA. Unlike siRNAs, miRNAs rarely form extensive numbers of base pairs to the mRNAs they regulate. We find that extensive complementarity between a target RNA and an Argonaute1-bound miRNA triggers miRNA tailing and 3'-to-5' trimming. In flies, Argonaute2-bound small RNAs--but not those bound to Argonaute1--bear a 2'-O-methyl group at their 3' ends. This modification blocks target-directed small RNA remodeling: In flies lacking Hen1, the enzyme that adds the 2'-O-methyl group, Argonaute2-associated siRNAs are tailed and trimmed. Target complementarity also affects small RNA stability in human cells. These results provide an explanation for the partial complementarity between animal miRNAs and their targets.

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    • "Uridylation has been coupled to target-dependent de-stabilization of small RNAs (Ameres et al., 2010), whereas adenylation has recently been shown to be involved in the clearance of maternal miRNAs (Lee et al., 2014). We therefore checked non-templated nucleotide addition in all bovine samples. "
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    • "Future studies should answer whether nonrandom miRNA release has a biological impact on gene regulation, which likely depends on multiple additional factors. Indeed, the level and function of mature miR- NAs are the result of different rates of both miRNA and target transcription, processing location, and turnover (Ameres et al., 2010; Baccarini et al., 2011). "
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    • "Yet, it is largely unknown, particularly in mammals, how cells control the quality of this elaborate and thus error-prone process . One quality control pathway for miRNAs and siRNAs in plants or flies is via decay of small RNAs that lack 2 0 -O-methylation in their 3 0 ends from Agos by noncanonical TUTs, such as HESO1 or MUT68 (Ameres et al., 2010; Ibrahim et al., 2010; Ren et al., 2012; Zhao et al., 2012). However, mammalian miRNAs are not methylated, and the relevance of this surveillance pathway for mammals is not apparent. "
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