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

Detrimental effects of RNAi: a cautionary note on its use in Drosophila ageing studies.
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DOI:
10.1371/journal.pone.0045367
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Partridge L
Partridge L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Alic N;Hoddinott MP;Foley A;Slack C;Piper MD;Partridge L

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RNA干扰(RNAi)为发现基因功能提供了重要工具。它已被广泛用于秀丽隐杆线虫衰老研究,因为它似乎对该模型生物体中的衰老相关性状没有任何非特异性影响。我们在此表明​​,通过表达靶向 GFP 或 lacZ 的双链 RNA 进行降解,或通过增加 Dicer 的表达来实现普遍存在的、成年发病的 RNAi 机制的激活,从而大大缩短果蝇的寿命。 GFPRNAi 构建体的诱导也会改变寿命对营养的反应,加剧含有大量酵母的食物的寿命缩短效应。我们的研究表明,RNAi 机制的激活可能会对寿命产生与序列无关的副作用,在果蝇衰老研究中使用普遍存在的 RNAi 时需要谨慎行事。然而,我们还表明,仅限于某些组织的 RNAi 可能不会损害寿命。
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.
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