Processing of Drosophila endo-siRNAs depends on a specific Loquacious isoform

Rui Zhou, Benjamin Czech, Julius Brennecke, Ravi Sachidanandam, James A. Wohlschlegel, Norbert Perrimon, Gregory J. Hannon

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Drosophila melanogaster expresses three classes of small RNAs, which are classified according to their mechanisms of biogenesis. MicroRNAs are ∼22-23 nucleotides (nt), ubiquitously expressed small RNAs that are sequentially processed from hairpin-like precursors by Drosha/Pasha and Dcr-1/Loquacious complexes. MicroRNAs usually associate with AGO1 and regulate the expression of protein-coding genes. Piwi-interacting RNAs (piRNAs) of ∼24-28 nt associate with Piwi-family proteins and can arise from single-stranded precursors. piRNAs function in transposon silencing and are mainly restricted to gonadal tissues. Endo-siRNAs are found in both germline and somatic tissues. These ∼21-nt RNAs are produced by a distinct Dicer, Dcr-2, and do not depend on Drosha/Pasha complexes. They predominantly bind to AGO2 and target both mobile elements and protein-coding genes. Surprisingly, a subset of endo-siRNAs strongly depend for their production on the dsRNA-binding protein Loquacious (Loqs), thought generally to be a partner for Dcr-1 and a cofactor for miRNA biogenesis. Endo-siRNA production depends on a specific Loqs isoform, Loqs-PD, which is distinct from the one, Loqs-PB, required for the production of microRNAs. Paralleling their roles in the biogenesis of distinct small RNA classes, Loqs-PD and Loqs-PB bind to different Dicer proteins, with Dcr-1/Loqs-PB complexes and Dcr-2/Loqs-PD complexes driving microRNA and endo-siRNA biogenesis, respectively.

Original languageEnglish (US)
Pages (from-to)1886-1895
Number of pages10
JournalRNA
Volume15
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

Keywords

  • Dicer
  • Double-stranded RNA-binding proteins (dsRBPs)
  • Drosophila melanogaster
  • Endo-siRNA processing
  • Loquacious
  • Transposon silencing

ASJC Scopus subject areas

  • Molecular Biology

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