Target RNA-directed tailing and trimming purifies the sorting of endo-siRNAs between the two Drosophila Argonaute proteins

Stefan L. Ameres, Jui-Hung Hung, Jia Xu, Zhiping Weng, Phillip D. Zamore

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

In flies, 22-23-nucleotide (nt) microRNA duplexes typically contain mismatches and begin with uridine, so they bind Argonaute1 (Ago1), whereas 21-nt siRNA duplexes are perfectly paired and begin with cytidine, promoting their loading into Ago2. A subset of Drosophila endogenous siRNAs-the hairpin-derived hp-esiRNAs-are born as mismatched duplexes that often begin with uridine. These would be predicted to load into Ago1, yet accumulate at steady-state bound to Ago2. In vitro, such hp-esiRNA duplexes assemble into Ago1. In vivo, they encounter complementary target mRNAs that trigger their tailing and trimming, causing Ago1-loaded hp-esiRNAs to be degraded. In contrast, Ago2-associated hp-esiRNAs are 29-O-methyl modified at their 39″ends, protecting them from tailing and trimming. Consequently, the steady-state distribution of esiRNAs reflects not only their initial sorting between Ago1 and Ago2 according to their duplex structure, length, and first nucleotide, but also the targeted destruction of the single-stranded small RNAs after their loading into an Argonaute protein.

Original languageEnglish
Pages (from-to)54-63
Number of pages10
JournalRNA
Volume17
Issue number1
DOIs
StatePublished - 1 Jan 2011

Keywords

  • Argonaute
  • MiRNA
  • MicroRNA
  • RNAi
  • Small RNA sorting

Fingerprint Dive into the research topics of 'Target RNA-directed tailing and trimming purifies the sorting of endo-siRNAs between the two Drosophila Argonaute proteins'. Together they form a unique fingerprint.

Cite this