Changing progeny’s inheritance

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Science Signaling  24 Feb 2015:
Vol. 8, Issue 365, pp. ec42
DOI: 10.1126/scisignal.aaa9612

Nematodes have mechanisms for transmitting “mobile” RNAs among somatic cells, and genes silenced with RNA interference techniques can be inherited as silenced in progeny (transgenerational gene silencing). Devanapally et al. determined that worms engineered to produce a double-stranded RNA (dsRNA) specifically in neurons delivered the dsRNA to the germline to produce transgenerational gene silencing for many subsequent generations. Worms engineered to express a dsRNA against green fluorescent protein (GFP) in neurons, but not those with the dsRNA in other somatic cells, reduced the GFP signal in the nuclei of germline cells expressing a nuclear targeted GFP. Crossing the worms with worms that were null for various components involved in mobile RNA transfer or dsRNA processing showed that the inheritable transfer required the dsRNA importer protein SID-1 and the Argonaute protein RDE-1, but was independent of other proteins involved in processing small RNAs. Maintenance of germline silencing required another Argonaute protein located in the nucleus HRDE-1, which mediates histone trimethylation, and MUT-7, an exonuclease, both of which are proteins required for heritable RNAi silencing. Why dsRNA from neurons is specifically competent to mediate transgenerational gene silencing is an open question.

S. Devanapally, S. Ravikumar, A. M. Jose, Double-stranded RNA made in C. elegans neurons can enter the germline and cause transgenerational gene silencing. Proc. Natl. Acad. Sci. U.S.A.112, 2133–2138 (2015). [PubMed]