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Small RNA

RNAi doesn't overdo it

Nature Reviews Genetics volume 14, pages 4–5 (2013)Cite this article

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dsRNA is cleaved by Dicer into primary short interfering RNAs (siRNAs), which guide Argonaute proteins to complementary sequences in endogenous RNAs, leading to target cleavage. In worms, plants and fungi, the primary siRNA–Argonaute complex also recruits RNA-directed RNA polymerases (RdRPs) that synthesize dsRNAs matching the endogenous target sequence. These dsRNAs are processed into secondary siRNAs, which amplify the gene-silencing effect.

Pak et al. sought to find out why the response does not amplify indefinitely by studying siRNA repertoires in C. elegans using high-throughput sequencing. To distinguish between primary and secondary siRNAs, they used a dsRNA trigger that included mismatches to the target gene (in this case, suppressor/enhancer of lin-12 (sel-1)). The primary siRNAs would contain the mismatch, but secondary RNAs would not. They found that most sel-1 siRNAs did not have the mismatches and were antisense to the target mRNA; this is consistent with these being secondary siRNAs that amplify the RNAi response.

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ORIGINAL RESEARCH PAPER

  1. Pak, J. et al. Protection from feed-forward amplification in an amplified RNAi mechanism. Cell 151, 885–899 (2012)

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  1. Mary Muers
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Muers, M. RNAi doesn't overdo it. Nat Rev Genet 14, 4–5 (2013). https://doi.org/10.1038/nrg3388

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