TY - JOUR
T1 - Detrimental effects of RNAi
T2 - a cautionary note on its use in drosophila ageing studies
AU - Alic, Nazif
AU - Hoddinott, Matthew P.
AU - Foley, Andrea
AU - Slack, Cathy
AU - Piper, Matthew D.W.
AU - Partridge, Linda
N1 - © 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.
PY - 2012/9/17
Y1 - 2012/9/17
N2 - 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.
AB - 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.
UR - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0045367
UR - http://www.scopus.com/inward/record.url?scp=84866460549&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0045367
DO - 10.1371/journal.pone.0045367
M3 - Article
C2 - 23028964
AN - SCOPUS:84866460549
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e45367
ER -