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Target accessibility dictates the potency of human RISC

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Abstract

In this report, we examined the effect of increased target site access on activated human RNA-induced silencing complex (RISC*) catalysis. Kinetic studies revealed that siRNA-programmed RISC* cleaved target RNA with higher efficiencies when target site access was increased. These results provide evidence that target site access is linked to RISC* catalysis.

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Figure 1: Target site access dictates the cleavage efficiency of siRISC*.
Figure 2: Kinetic analysis of human siRISC* programmed by siRNA targeting Cdk9 mRNA.

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Acknowledgements

We thank members of the Rana lab, C. Mello and P. Zamore for helpful discussions; T.J. Richman for editorial assistance; and H. Cao for kinetic data analysis. This work was supported in part by grants from the US National Institutes of Health (AI 41404 and AI 43198) to T.M.R.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, 01605, Massachusetts, USA

    Kirk M Brown, Chia-ying Chu & Tariq M Rana

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  1. Kirk M Brown
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  2. Chia-ying Chu
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  3. Tariq M Rana
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Correspondence to Tariq M Rana.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Cdk9 RISC concentration. (PDF 295 kb)

Supplementary Fig. 2

GFP RISC kinetics. (PDF 209 kb)

Supplementary Fig. 3

GFP and Cdk9 initial velocity. (PDF 495 kb)

Supplementary Methods (PDF 27 kb)

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Brown, K., Chu, Cy. & Rana, T. Target accessibility dictates the potency of human RISC. Nat Struct Mol Biol 12, 469–470 (2005). https://doi.org/10.1038/nsmb931

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  • DOI: https://doi.org/10.1038/nsmb931

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