Skip Navigation



Nucleic Acids Research Advance Access published online on September 28, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm663
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (1095K) Freely available
Right arrow Screen PDF (593K) Freely available
Right arrow Supplementary Material
Right arrow Supplementary Material
Right arrow Supplementary Material
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
35/19/6598    most recent
gkm663v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Vickers, T. A.
Right arrow Articles by Crooke, S. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vickers, T. A.
Right arrow Articles by Crooke, S. T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

RNA

Reduced levels of Ago2 expression result in increased siRNA competition in mammalian cells

Timothy A. Vickers*, Walt F. Lima, Josh G. Nichols and Stanley T. Crooke

Isis Pharmaceuticals. 1896 Rutherford Road, Carlsbad, CA 92008, USA

*To whom correspondence should be addressed. Tel: 760 931 9200; Fax: 760 268 4989; Email: tvickers{at}isisph.com

Received July 13, 2007. Revised August 9, 2007. Accepted August 10, 2007.

Administration of small interfering RNAs (siRNAs) leads to degradation of specific mRNAs utilizing the cellular RNA interference (RNAi) machinery. It has been demonstrated that co-administration of siRNAs may lead to attenuation of activity of one of the siRNAs. Utilizing antisense and siRNA-mediated RNA-induced silencing complex (RISC) gene reduction we show that siRNA competition is correlated with differences in the cellular expression levels of Ago2, while levels of other RISC proteins have no effect on competition. We also show that under certain conditions siRNA competition rather than reduction of cellular RISC levels may be responsible for apparent reduction in siRNA activity. Furthermore, exploiting siRNA competition, we show that the RISC pathway loads and results in detectable cleavage of the target RNA in ~2 h after transfection. The RISC pathway is also capable of being reloaded even in the absence of new protein synthesis. RISC reloading and subsequent induction of detectable cleavage of a new target RNA, requires about 9–12 h following the initial transfection.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
L. L. Snyder, I. Ahmed, and L. F. Steel
RNA polymerase III can drive polycistronic expression of functional interfering RNAs designed to resemble microRNAs
Nucleic Acids Res., October 1, 2009; 37(19): e127 - e127.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
W. F. Lima, H. Murray, J. G. Nichols, H. Wu, H. Sun, T. P. Prakash, A. R. Berdeja, H. J. Gaus, and S. T. Crooke
Human Dicer Binds Short Single-strand and Double-strand RNA with High Affinity and Interacts with Different Regions of the Nucleic Acids
J. Biol. Chem., January 23, 2009; 284(4): 2535 - 2548.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
Z. Li, Y. Fortin, and S.-H. Shen
Forward and robust selection of the most potent and noncellular toxic siRNAs from RNAi libraries
Nucleic Acids Res., January 1, 2009; 37(1): e8 - e8.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. M. Hasan, M. J. Longacre, S. W. Stoker, T. Boonsaen, S. Jitrapakdee, M. A. Kendrick, J. C. Wallace, and M. J. MacDonald
Impaired Anaplerosis and Insulin Secretion in Insulinoma Cells Caused by Small Interfering RNA-mediated Suppression of Pyruvate Carboxylase
J. Biol. Chem., October 17, 2008; 283(42): 28048 - 28059.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.