Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/179398
Title: | RNA major groove modifications improve siRNA stability and biological activity |
Author: | Terrazas Martínez, Montserrat Kool, Eric T. |
Keywords: | RNA Química orgànica Oligonucleòtids RNA Organic chemistry Oligonucleotides |
Issue Date: | Feb-2009 |
Publisher: | Oxford University Press |
Abstract: | RNA 5-methyl and 5-propynyl pyrimidine analogs were substituted into short interfering RNAs (siRNAs) to probe major groove steric effects in the active RNA-induced silencing complex (RISC). Synthetic RNA guide strands containing varied combinations of propynyl and methyl substitution revealed that all C-5 substitutions increased the thermal stability of siRNA duplexes containing them. Cellular gene suppression experiments using luciferase targets in HeLa cells showed that the bulky 5-propynyl modification was detrimental to RNA interference activity, despite its stabilization of the helix. Detrimental effects of this substitution were greatest at the 5′-half of the guide strand, suggesting close steric approach of proteins in the RISC complex with that end of the siRNA/mRNA duplex. However, substitutions with the smaller 5-methyl group resulted in gene silencing activities comparable to or better than that of wild-type siRNA. The major groove modifications also increased the serum stability of siRNAs. |
Note: | Reproducció del document publicat a: https://doi.org/10.1093/nar/gkn958 |
It is part of: | Nucleic Acids Research, 2009, vol. 37, num. 2, p. 346-353 |
URI: | http://hdl.handle.net/2445/179398 |
Related resource: | https://doi.org/10.1093/nar/gkn958 |
ISSN: | 0305-1048 |
Appears in Collections: | Articles publicats en revistes (Química Inorgànica i Orgànica) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
713436.pdf | 3.71 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License