Identification and Characterization of C. elegans RNAi Inheritance Mac

Small RNAs can regulate gene expression in eukaryotes. During RNA interference (RNAi), small RNAs are bound by Argonaute proteins and act as guide molecules to silence cellular RNAs. In C. elegans, RNAi silencing can persist for 6-10 generations in the absence of the initial trigger (termed RNAi inheritance). RNAi inheritance requires the nuclear RNAi factors NRDE-1/-2/-4 highlighting the importance of co-transcriptional gene silencing and heterochromatin formation in heritable gene silencing by dsRNA. This thesis explores how gene silencing propagates across generations by identifying and characterizing cellular factors required for RNAi inheritance in the model organism C. elegans. Chapter 2 of this thesis identifies six novel components of the RNAi inheritance machinery whose sequence conservation provides insights into the molecular mechanism of RNAi inheritance and strengthens the correlation between RNAi inheritance and germline immortality. Chapter 2 also demonstrates that HRDE-2 promotes RNAi inheritance by coupling the inheritance Ago HRDE-1 with the small RNAs it needs to direct RNAi inheritance and germline immortality.