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Detrimental effects of RNAi: a cautionary note on its use in Drosophila ageing studies

Alic, N; Hoddinott, MP; Foley, A; Slack, C; Piper, MD; Partridge, L; (2012) Detrimental effects of RNAi: a cautionary note on its use in Drosophila ageing studies. PLOS One , 7 (9) , Article e45367. 10.1371/journal.pone.0045367. Green open access

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Abstract

RNA interference (RNAi) provides an important tool for gene function discovery. It has been widely exploited in Caenorhabditis elegans ageing research because it does not appear to have any non-specific effects on ageing-related traits in that model organism. We show here that ubiquitous, adult-onset activation of the RNAi machinery, achieved by expressing a double stranded RNA targeting GFP or lacZ for degradation, or by increasing expression of Dicer substantially reduces lifespan in Drosophila melanogaster. Induction of GFPRNAi construct also alters the response of lifespan to nutrition, exacerbating the lifespan-shortening effects of food containing a high quantity of yeast. Our study indicates that activation of the RNAi machinery may have sequence-independent side-effects on lifespan, and that caution needs to be exercised when employing ubiquitous RNAi in Drosophila ageing studies. However, we also show that RNAi restricted to certain tissues may not be detrimental to lifespan.

Type: Article
Title: Detrimental effects of RNAi: a cautionary note on its use in Drosophila ageing studies
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0045367
Publisher version: http://dx.doi.org/10.1371/journal.pone.0045367
Language: English
Additional information: © Alic et al. 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 credited. This work was funded by the Wellcome Trust and Max Planck (L.P.) and Excellence in Life Sciences (EMBO) and Marie Currie Fellowships (N.A.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: http://discovery.ucl.ac.uk/id/eprint/1370027
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