Cited by 499

Fragile X-related protein and VIG associate with the RNA interference machinery

Caudy, Amy A., Myers, Mike, Hannon, Gregory J., Hammond, Scott M.·2002·Genes & Development

Abstract

RNA interference (RNAi) is a flexible gene silencing mechanism that responds to double-stranded RNA by suppressing homologous genes. Here, we report the characterization of RNAi effector complexes (RISCs) that contain small interfering RNAs and microRNAs (miRNAs). We identify two putative RNA-binding proteins, the Drosophila homolog of the fragile X mental retardation protein (FMRP), dFXR, and VIG (Vasa intronic gene), through their association with RISC. FMRP, the product of the human fragile X locus, regulates the expression of numerous mRNAs via an unknown mechanism. The possibility that dFXR, and potentially FMRP, use, at least in part, an RNAi-related mechanism for target recognition suggests a potentially important link between RNAi and human disease.

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  • FMRP-associated miRNAs 125b and 132 modulate dendritic spine morphology together with FMRP through common mRNA targets.

    “Since FMRP is not needed for general RNAi function (Caudy et al., 2002; Hock et al., 2007), these findings support the idea that the FMRP-associated miRNAs 125b and 132 modulate dendritic spine morphology together with FMRP through common mRNA targets.”
  • The lack of a canonical miRNA/siRNA binding domain in FMRP suggests that miRNAs are indirectly associated with FMRP, possibly through Argonaute proteins.

    “The lack of a canonical miRNA/siRNA binding domain in FMRP suggests that miRNAs are indirectly associated with FMRP, possibly through Argonaute proteins which contain a miRNA binding domain and interact with FMRP in an RNA-independent manner (Caudy et al., 2002; Ishizuka et al., 2002).”
  • FMRP interacts with proteins in RISC and with miRNAs, but FMRP itself is not essential for RNAi-mediated mRNA cleavage.

    “FMRP interacts with proteins (e.g. Argonaute and Dicer) in the RNA interference silencing complex (RISC) and with miRNAs, but FMRP itself is not essential for RNAi-mediated mRNA cleavage (Bolduc et al., 2008; Caudy et al., 2002; Cheever and Ceman, 2009; Hock et al., 2007; Ishizuka et al., 2002; Jin et al., 2004b; Okamura et al., 2004; Plante et al., 2006).”

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Research works printed but not linked: 5

  1. Dudley, N.R., Labbe, J.C., and Goldstein, B. 2002. Using RNA interfer- ence to identify genes required for RNA interference. Proc. Natl. Acad. Sci. 99: 4191-4196.
  2. Hutvágner, G. and Zamore, P.D. 2002. A MicroRNA in a multiple-turn- over RNAi enzyme complex. Science (in press).
  3. Ketting, R.F., Fischer, S.E., Bernstein, E., Sijen, T., Hannon, G.J., and Plasterk, R.H. 2001. Dicer functions in RNA interference and in syn- thesis of small RNA involved in developmental timing in C. elegans. Genes & Dev. 15: 2654-2659.
  4. Paddison, P.J., Caudy, A.A., and Hannon, G.J. 2002. Stable suppression of gene expression by RNAi in mammalian cells. Proc. Natl Acad Sci. 99: 1443-1448.
  5. Williams, R.W. and Rubin, G.M. 2002. ARGONAUTE1 is required for efficient RNA interference in Drosophila embryos. Proc. Natl. Acad. Sci. 99: 6889-6894.

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Authors
Caudy, A. A., Myers, M., Hannon, G. J., & Hammond, S. M.
Venue
Genes & Development
Published
2002-10-01
Volume
16
Issue
19
Pages
2491-2496
ISSN
  • 0890-9369
  • 1549-5477
Cited by
499
References
1
Language
en

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