MRNA turnover rate limits siRNA and microRNA efficacy Journal Article
| Authors: | Larsson, E.; Sander, C.; Marks, D. |
| Article Title: | 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 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 RTĝ€"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. © 2010 EMBO and Macmillan Publishers Limited. All rights reserved. |
| Keywords: | genetics; polymerase chain reaction; metabolism; reverse transcription polymerase chain reaction; microrna; gene expression; biological model; cell line; small interfering rna; rna, small interfering; genetic association; rna interference; validation study; hela cell; hela cells; messenger rna; rna, messenger; models, genetic; rna stability; micrornas; half life time; short hairpin rna; half-life; cell strain hepg2; rnai; sirna; mrna decay; turnover time |
| Journal Title: | Molecular Systems Biology |
| Volume: | 6 |
| ISSN: | 1744-4292 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2010-11-16 |
| Start Page: | 433 |
| Language: | English |
| DOI: | 10.1038/msb.2010.89 |
| PUBMED: | 21081925 |
| PROVIDER: | scopus |
| PMCID: | PMC3010119 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "Article No: 433" - "Source: Scopus" |
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