Early Developmental Exposure to dsRNA Is Critical for Initiating Efficient Nuclear RNAi in C. elegans

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Philip K. Shiu, Craig P. Hunter
RNAi has enabled researchers to study the function of many genes. However, it is not understood why some RNAi experiments succeed while others do not. Here, we show in C. elegans that pharyngeal muscle is resistant to RNAi when initially exposed to double-stranded RNA (dsRNA) by feeding but sensitive to RNAi in the next generation. Investigating this observation, we find that pharyngeal muscle cells as well as vulval muscle cells require nuclear rather than cytoplasmic RNAi. Further, we find in these cell types that nuclear RNAi silencing is most efficiently triggered during early development, defining a critical period for initiating nuclear RNAi. Finally, using heat-shock-induced dsRNA expression, we show that synMuv B class mutants act in part to extend this critical window. The synMuv-B-dependent early-development-associated critical period for initiating nuclear RNAi suggests that mechanisms that restrict developmental plasticity may also restrict the initiation of nuclear RNAi.

Graphical abstract

Teaser

C. elegans investigators have found that the progeny of worms fed double-stranded RNA often have stronger RNAi phenotypes than the parental generation. Shiu and Hunter show that this is explained, for some tissues, by a necessity for nuclear RNAi, which requires dsRNA exposure during an early critical period.


http://ift.tt/2n5HHe8