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DC Field | Value | Language |
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dc.contributor.author | Terrazas Martínez, Montserrat | - |
dc.contributor.author | Kool, Eric T. | - |
dc.date.accessioned | 2021-07-27T07:33:33Z | - |
dc.date.available | 2021-07-27T07:33:33Z | - |
dc.date.issued | 2009-02 | - |
dc.identifier.issn | 0305-1048 | - |
dc.identifier.uri | http://hdl.handle.net/2445/179398 | - |
dc.description.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. | - |
dc.format.extent | 8 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Oxford University Press | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1093/nar/gkn958 | - |
dc.relation.ispartof | Nucleic Acids Research, 2009, vol. 37, num. 2, p. 346-353 | - |
dc.relation.uri | https://doi.org/10.1093/nar/gkn958 | - |
dc.rights | cc-by-nc (c) Terrazas Martínez, Montserrat et al., 2009 | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | - |
dc.source | Articles publicats en revistes (Química Inorgànica i Orgànica) | - |
dc.subject.classification | RNA | - |
dc.subject.classification | Química orgànica | - |
dc.subject.classification | Oligonucleòtids | - |
dc.subject.other | RNA | - |
dc.subject.other | Organic chemistry | - |
dc.subject.other | Oligonucleotides | - |
dc.title | RNA major groove modifications improve siRNA stability and biological activity | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 713436 | - |
dc.date.updated | 2021-07-27T07:33:33Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 19042976 | - |
Appears in Collections: | Articles publicats en revistes (Química Inorgànica i Orgànica) |
Files in This Item:
File | Description | Size | Format | |
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713436.pdf | 3.71 MB | Adobe PDF | View/Open |
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