mRNA turnover rate limits siRNA and microRNA efficacy
Abstract The microRNA pathway participates in basic cellular processes and its discovery has enabled the development of si/shRNAs as powerful investigational tools and potential therapeutics. Based on a simple kinetic model of the mRNA life cycle, we hypothesized that mRNAs with high turnover rates...
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| Format: | Article |
| Language: | English |
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Springer Nature
2010-11-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2010.89 |
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| _version_ | 1849225747417268224 |
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| author | Erik Larsson Chris Sander Debora Marks |
| author_facet | Erik Larsson Chris Sander Debora Marks |
| author_sort | Erik Larsson |
| collection | DOAJ |
| description | Abstract The microRNA pathway participates in basic cellular processes and its discovery has enabled the development of si/shRNAs as powerful investigational tools and potential therapeutics. Based on a simple kinetic model of the mRNA life cycle, we hypothesized that mRNAs with high turnover rates may be more resistant to RNAi‐mediated silencing. The results of a simple reporter experiment strongly supported this hypothesis. We followed this with a genome‐wide scale analysis of a rich corpus of experiments, including RT–qPCR validation data for thousands of siRNAs, siRNA/microRNA overexpression data and mRNA stability data. We find that short‐lived transcripts are less affected by microRNA overexpression, suggesting that microRNA target prediction would be improved if mRNA turnover rates were considered. Similarly, short‐lived transcripts are more difficult to silence using siRNAs, and our results may explain why certain transcripts are inherently recalcitrant to perturbation by small RNAs. |
| format | Article |
| id | doaj-art-20ee8a29b51442f096cd8c2ae57b72cc |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2010-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-20ee8a29b51442f096cd8c2ae57b72cc2025-08-24T12:00:02ZengSpringer NatureMolecular Systems Biology1744-42922010-11-01611910.1038/msb.2010.89mRNA turnover rate limits siRNA and microRNA efficacyErik Larsson0Chris Sander1Debora Marks2Computational Biology Center, Memorial Sloan Kettering Cancer CenterComputational Biology Center, Memorial Sloan Kettering Cancer CenterDepartment of Systems Biology, Harvard Medical SchoolAbstract The microRNA pathway participates in basic cellular processes and its discovery has enabled the development of si/shRNAs as powerful investigational tools and potential therapeutics. Based on a simple kinetic model of the mRNA life cycle, we hypothesized that mRNAs with high turnover rates may be more resistant to RNAi‐mediated silencing. The results of a simple reporter experiment strongly supported this hypothesis. We followed this with a genome‐wide scale analysis of a rich corpus of experiments, including RT–qPCR validation data for thousands of siRNAs, siRNA/microRNA overexpression data and mRNA stability data. We find that short‐lived transcripts are less affected by microRNA overexpression, suggesting that microRNA target prediction would be improved if mRNA turnover rates were considered. Similarly, short‐lived transcripts are more difficult to silence using siRNAs, and our results may explain why certain transcripts are inherently recalcitrant to perturbation by small RNAs.https://doi.org/10.1038/msb.2010.89microRNAmRNA decayRNAisiRNA |
| spellingShingle | Erik Larsson Chris Sander Debora Marks mRNA turnover rate limits siRNA and microRNA efficacy Molecular Systems Biology microRNA mRNA decay RNAi siRNA |
| title | mRNA turnover rate limits siRNA and microRNA efficacy |
| title_full | mRNA turnover rate limits siRNA and microRNA efficacy |
| title_fullStr | mRNA turnover rate limits siRNA and microRNA efficacy |
| title_full_unstemmed | mRNA turnover rate limits siRNA and microRNA efficacy |
| title_short | mRNA turnover rate limits siRNA and microRNA efficacy |
| title_sort | mrna turnover rate limits sirna and microrna efficacy |
| topic | microRNA mRNA decay RNAi siRNA |
| url | https://doi.org/10.1038/msb.2010.89 |
| work_keys_str_mv | AT eriklarsson mrnaturnoverratelimitssirnaandmicrornaefficacy AT chrissander mrnaturnoverratelimitssirnaandmicrornaefficacy AT deboramarks mrnaturnoverratelimitssirnaandmicrornaefficacy |