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Title: RNA major groove modifications improve siRNA stability and biological activity
Author: Terrazas Martínez, Montserrat
Kool, Eric T.
Keywords: RNA
Química orgànica
Organic chemistry
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.
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It is part of: Nucleic Acids Research, 2009, vol. 37, num. 2, p. 346-353
Related resource:
ISSN: 0305-1048
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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