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Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans

Ketting, René F., Fischer, Sylvia E.J., Bernstein, Emily, Sijen, Titia, Hannon, Gregory J., Plasterk, Ronald H.A.·2001·Genes & Development

Abstract

Double-stranded RNAs can suppress expression of homologous genes through an evolutionarily conserved process named RNA interference (RNAi) or post-transcriptional gene silencing (PTGS). One mechanism underlying silencing is degradation of target mRNAs by an RNP complex, which contains ∼22 nt of siRNAs as guides to substrate selection. A bidentate nuclease called Dicer has been implicated as the protein responsible for siRNA production. Here we characterize the Caenorhabditis elegans ortholog of Dicer ( K12H4.8 ; dcr-1 ) in vivo and in vitro. dcr-1 mutants show a defect in RNAi. Furthermore, a combination of phenotypic abnormalities and RNA analysis suggests a role for dcr-1 in a regulatory pathway comprised of small temporal RNA ( let-7 ) and its target (e.g., lin-41 ).

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  1. Anandalakshmi, R., Pruss, G.J., Ge, X., Marathe, R., Mallory, A.C., Smith, T.H., and Vance, V.B. 1998. A viral suppressor of gene silenc- ing in plants. Proc. Natl. Acad. Sci. 95: 13079-13084.
  2. Chuang, C.F. and Meyerowitz, E.M. 2000. Specific and heritable genetic interference by double-stranded RNA in Arabidopsis thaliana. Proc. Natl. Acad. Sci. 97: 4985-4990.
  3. Knight, S.W. and Bass, B.L. 2001. A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in C. elegans. [Pub- lished online 2 August/10.1126/Science 1062039] · DOI · Paper page
  4. Napoli, C., Lemieux, C., and Jorgensen, R.A. 1990. Introduction of a chimeric chalcone synthase gene into Petunia results in reversible co-suppression of homologous genes in trans. Plant Cell 2: 279-289.
  5. Voinnet, O., Pinto, Y.M., and Baulcombe, D.C. 1999. Suppression of gene silencing: A general strategy used by diverse DNA and RNA viruses of plants. Proc. Natl. Acad. Sci. 96: 14147-14152.

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Authors
Ketting, R. F., Fischer, S. E. J., Bernstein, E., Sijen, T., Hannon, G. J., & Plasterk, R. H. A.
Venue
Genes & Development
Published
2001-10-15
Volume
15
Issue
20
Pages
2654-2659
ISSN
  • 0890-9369
  • 1549-5477
Cited by
1,527
References
0
Language
en

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