Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Target accessibility dictates the potency of human RISC

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

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

Similar content being viewed by others

References

  1. Fire, A., et al. Nature 391, 806–811 (1998).

    Article  CAS  PubMed  Google Scholar 

  2. Song, J.J. et al. Science 305, 1434–1437 (2004).

    Article  CAS  PubMed  Google Scholar 

  3. Liu, J. et al. Science 305, 1437–1441 (2004).

    Article  CAS  PubMed  Google Scholar 

  4. Meister, G. et al. Mol. Cell 15, 185–197 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Hutvagner, G. & Zamore, P.D. Science 297, 2056–2060 (2002).

    Article  CAS  PubMed  Google Scholar 

  6. Rana, T.M. & Jeang, K.T. Arch. Biochem. Biophys. 365, 175–185 (1999).

    Article  CAS  PubMed  Google Scholar 

  7. Hutvagner, G. et al. PLoS Biol. 2, E98 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kozak, M. Gene 234, 187–208 (1999).

    Article  CAS  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tariq M Rana.

Ethics declarations

Competing interests

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)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing