Reconstitution of an Argonaute-Dependent Small RNA Biogenesis Pathway Reveals a Handover Mechanism Involving the RNA Exosome and the Exonuclease QIP

Zhihong Xue, Haiyan Yuan, Jinhu Guo, Yi Liu

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Argonaute proteins are required for the biogenesis of some small RNAs (sRNAs), including the PIWI-interacting RNAs and some microRNAs. How Argonautes mediate maturation of sRNAs independent of their slicer activity is not clear. The maturation of the . Neurospora microRNA-like sRNA, milR-1, requires the Argonaute protein QDE-2, Dicer, and QIP. Here, we reconstitute this Argonaute-dependent sRNA biogenesis pathway in vitro and discover that the RNA exosome is also required for milR-1 production. Our results demonstrate that QDE-2 mediates milR-1 maturation by recruiting exosome and QIP and by determining the size of milR-1. The exonuclease QIP first separates the QDE-2-bound pre-milR-1 duplex and then mediates 3' to 5' trimming and maturation of pre-milRNA together with exosome using a handover mechanism. In addition, exosome is also important for the decay of sRNAs. Together, our results establish a biochemical mechanism of an Argonaute-dependent sRNA biogenesis pathway and critical roles of exosome in sRNA processing.

Original languageEnglish (US)
Pages (from-to)299-310
Number of pages12
JournalMolecular cell
Volume46
Issue number3
DOIs
StatePublished - May 11 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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