Some years ago Hiroaki Kawasaki and Kazunari Taira published an article called "Induction of DNA methylation and gene silencing by short interfering RNAs in human cells" in Nature:

In plants, dsRNAs targeted to CpG islands within a promoter can also induce RNA-directed DNA methylation3, 4, 5, 6, 7, 8; however, it remains unclear whether gene silencing mediated by DNA methylation can be induced by dsRNAs in mammalian cells. Here, we demonstrate that short interfering RNAs (siRNAs; 21–25-nucleotide RNA molecules) induce DNA methylation and histone H3 methylation in human cells.

This paper seemed to show that siRNA can also induce long-term silencing of genes by DNA methylation in mammalian cells, which hasn't previously been observed. Unfortunately, the paper was retracted later, calling the results into question.

I found the paper very exciting at the time, as it suggested the possibility to perform gene therapy, to silence specficic genes, just by using RNA interference.

What is the current scientific consensus here, is there any convincing evidence that siRNA-induced DNA methylation is possible in mammalian cells? Was anyone able to replicate the results from Kawasaki and Taira?


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From a brief survey of the literature, it seems Kawasaki and Taira have been largely vindicated by the community before and since their paper. The retraction was by Taira alone, Kawasaki refused to co-sign because he maintained the data were valid. From the retraction it seems the reason for the retraction was a lost lab book.

Prior to the Kawasaki and Taiga paper, there were already several other papers describing RNAi-induced epigenetic modification in mammals:

Then there was another paper the next year by Kawasaki & Taira, which was not retracted:

And it seems the idea is now generally accepted and supported by quite a few other studies, mainly looking at germline cells. For example:

There is no review that I could find which really ties it all together convincingly, but there are several reviews on RNAi directed histone and chromatin modification in general which mention that the fact is now established in mammals:

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    $\begingroup$ The germ cell reference (Carmell et al., 2007) does not describe siRNA, instead it deals with entirely different class of small RNAs, called piRNA (in the paper they referred to them as rasiRNA, but piRNA now is a commonly used nomenclature). There are crucial differences between siRNA and piRNA (size distributions and proteins with which they associate) and they shouldn't be mixed up. $\endgroup$
    – Sergei
    Feb 20, 2015 at 16:50
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    $\begingroup$ I browsed through Joshua-Tor and Hannon (2010) review that you cited and I haven't noticed any mentioning of siRNAs directing DNA methylation (or histone modification) in mammals. Sorry if I missed it, can you please quote the relevant sentence? $\endgroup$
    – Sergei
    Feb 20, 2015 at 16:53
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    $\begingroup$ @Sergei you're right! That paper actually mentions piRNA-directed methylation, rather than siRNA. I'll leave it in the answer as it is still of relevance to the question. $\endgroup$ Feb 21, 2015 at 9:11

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