Early Developmental Exposure to dsRNA Is Critical for Initiating Efficient Nuclear RNAi in C. elegans.
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.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Philip K
PK
Shiu
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: hunter@mcb.harvard.edu.
Craig P
CP
Hunter
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D020868:Gene Silencing / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000502:physiology; D009154:Mutation / Q000235:genetics; D010614:Pharynx / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D034622:RNA Interference / Q000187:drug effects*; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D014844:Vulva / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D012330:RNA, Double-Stranded
RNAi; Rb; critical period; enhanced RNAi; nuclear RNAi