2006-06-01

[进展]RNAi并不参与反义核苷酸介导的基因表达调控

哺乳动物中,RNAi并不参与反义核苷酸介导的基因表达调控。

反义转录同时产生编码和非编码的RNA,这是哺乳动物中的普遍现象。自然反义转录(NAT)调控基因表达的机理,在很大程度上是未知的。本研究的目的就是,通过研究编码和非编码NAT对相应基因表达的作用,来探索正义-反义之间的相互调控机理,并探讨内源性RNAi在正反义相互作用中的可能作用。

他们分别以具有正反义NAT的内源基因:胸腺嘧啶合酶和缺氧诱导引子1α为例,检测了它们的正反义RNA的配对机制。以前普遍认为正反义RNA在胞质中形成二体,并激活随后的RNAi,但是他们在这里提供了直接的证据来反对这个看法。

总之,他们的数据表明,NAT对基因表达的调控是发生于一个独立通路上的,它和Dicer酶相关的RNAi没有关系。并且,他们也引入了一个实验策略,可用于其他的正反义RNA对之间的相互作用的功能检测。

(发表于Genome Biology 2006, 7:R38 doi:10.1186/gb-2006-7-5-r38,http://genomebiology.com/2006/7/5/R38

英文摘要对照:

Background

Antisense transcription, yielding both coding and non-coding RNA, is a widespread phenomenon in mammals. The mechanism by which natural antisense transcripts (NAT) may regulate gene expression are largely unknown. The aim of the present study was to explore the mechanism of reciprocal sense-antisense (S-AS) regulation by studying the effects of a coding and non-coding NAT on corresponding gene expression, and to investigate the possible involvement of endogenous RNA interference (RNAi) in S-AS interactions.

Results

We have examined the mechanism of S-AS RNA base pairing, using thymidylate synthase and hypoxia inducible factor-1α as primary examples of endogenous genes with coding and non-coding NAT partners, respectively. Here we provide direct evidence against S-AS RNA duplex formation in the cytoplasm of human cells and subsequent activation of RNAi.

Conclusion

Collectively, our data demonstrate that NAT regulation of gene expression occurs through a pathway independent of Dicer associated RNAi. Moreover, we introduce an experimental strategy with utility for the functional examination of other S-AS pair interactions.

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