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Modeling Recursive RNA Interference

An important application of the RNA interference (RNAi) pathway is its use as a small RNA-based regulatory system commonly exploited to suppress expression of target genes to test their function in vivo. In several published experiments, RNAi has been used to inactivate components of the RNAi pathwa...

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Autor principal: Marshall, Wallace F.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2522276/
https://www.ncbi.nlm.nih.gov/pubmed/18802453
http://dx.doi.org/10.1371/journal.pcbi.1000183
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author Marshall, Wallace F.
author_facet Marshall, Wallace F.
author_sort Marshall, Wallace F.
collection PubMed
description An important application of the RNA interference (RNAi) pathway is its use as a small RNA-based regulatory system commonly exploited to suppress expression of target genes to test their function in vivo. In several published experiments, RNAi has been used to inactivate components of the RNAi pathway itself, a procedure termed recursive RNAi in this report. The theoretical basis of recursive RNAi is unclear since the procedure could potentially be self-defeating, and in practice the effectiveness of recursive RNAi in published experiments is highly variable. A mathematical model for recursive RNAi was developed and used to investigate the range of conditions under which the procedure should be effective. The model predicts that the effectiveness of recursive RNAi is strongly dependent on the efficacy of RNAi at knocking down target gene expression. This efficacy is known to vary highly between different cell types, and comparison of the model predictions to published experimental data suggests that variation in RNAi efficacy may be the main cause of discrepancies between published recursive RNAi experiments in different organisms. The model suggests potential ways to optimize the effectiveness of recursive RNAi both for screening of RNAi components as well as for improved temporal control of gene expression in switch off–switch on experiments.
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spelling pubmed-25222762008-09-19 Modeling Recursive RNA Interference Marshall, Wallace F. PLoS Comput Biol Research Article An important application of the RNA interference (RNAi) pathway is its use as a small RNA-based regulatory system commonly exploited to suppress expression of target genes to test their function in vivo. In several published experiments, RNAi has been used to inactivate components of the RNAi pathway itself, a procedure termed recursive RNAi in this report. The theoretical basis of recursive RNAi is unclear since the procedure could potentially be self-defeating, and in practice the effectiveness of recursive RNAi in published experiments is highly variable. A mathematical model for recursive RNAi was developed and used to investigate the range of conditions under which the procedure should be effective. The model predicts that the effectiveness of recursive RNAi is strongly dependent on the efficacy of RNAi at knocking down target gene expression. This efficacy is known to vary highly between different cell types, and comparison of the model predictions to published experimental data suggests that variation in RNAi efficacy may be the main cause of discrepancies between published recursive RNAi experiments in different organisms. The model suggests potential ways to optimize the effectiveness of recursive RNAi both for screening of RNAi components as well as for improved temporal control of gene expression in switch off–switch on experiments. Public Library of Science 2008-09-19 /pmc/articles/PMC2522276/ /pubmed/18802453 http://dx.doi.org/10.1371/journal.pcbi.1000183 Text en Wallace F. Marshall. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Marshall, Wallace F.
Modeling Recursive RNA Interference
title Modeling Recursive RNA Interference
title_full Modeling Recursive RNA Interference
title_fullStr Modeling Recursive RNA Interference
title_full_unstemmed Modeling Recursive RNA Interference
title_short Modeling Recursive RNA Interference
title_sort modeling recursive rna interference
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2522276/
https://www.ncbi.nlm.nih.gov/pubmed/18802453
http://dx.doi.org/10.1371/journal.pcbi.1000183
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