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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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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2008
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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. |
format | Text |
id | pubmed-2522276 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT marshallwallacef modelingrecursivernainterference |