A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins

Akira Ishizuka, Mikiko C. Siomi, Haruhiko Siomi

Research output: Contribution to journalArticlepeer-review

466 Citations (Scopus)

Abstract

Fragile X syndrome is a common form of inherited mental retardation caused by the loss of FMR1 expression. The FMR1 gene encodes an RNA-binding protein that associates with translating ribosomes and acts as a negative translational regulator. In Drosophila, the fly homolog of the FMR1 protein (dFMR1) binds to and represses the translation of an mRNA encoding of the microtuble-associated protein Futsch. We have isolated a dFMR1-associated complex that includes two ribosomal proteins, L5 and Lll, along with 5S RNA. The dFMR1 complex also contains Argonaute2 (AGO2) and a Drosophila homolog of p68 RNA helicase (Dmp68). AGO2 is an essential component for the RNA-induced silencing complex (RISC), a sequence-specific nuclease complex that mediates RNA interference (RNAi) in Drosophila. We show that Dmp68 is also required for efficient RNAi. We further show that dFMR1 is associated with Dicer, another essential component of the RNAi pathway, and microRNAs (miRNAs) in vivo, suggesting that dFMR1 is part of the RNAi-related apparatus. Our findings suggest a model in which the RNAi and dFMR1-mediated translational control pathways intersect in Drosophila. Our findings also raise the possibility that defects in an RNAi-related machinery may cause human disease.

Original languageEnglish
Pages (from-to)2497-2508
Number of pages12
JournalGenes and Development
Volume16
Issue number19
DOIs
Publication statusPublished - 2002 Oct 1
Externally publishedYes

Keywords

  • FMR1
  • Fragile X syndrome
  • MiRNA
  • RNA helicase
  • RNAi

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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