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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/179398
RNA major groove modifications improve siRNA stability and biological activity
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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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TERRAZAS MARTÍNEZ, Montserrat, KOOL, Eric t.. RNA major groove modifications improve siRNA stability and biological activity. _Nucleic Acids Research_. 2009. Vol. 37, núm. 2, pàgs. 346-353. [consulta: 24 de gener de 2026]. ISSN: 0305-1048. [Disponible a: https://hdl.handle.net/2445/179398]