Genetic regulation of RNAi inheritance in the Caenorhabditis elegans germ line

Small RNAs can regulate the expression of other cellular RNAs. RNA interference is a process by which small RNAs `silence' genes by inhibiting transcription or degrading messenger RNAs, preventing the gene from making functional products. RNAi induced silencing is epigenetic, the DNA sequence is left unaltered. Interestingly, RNAi induced silencing can be heritable for multiple generations. The nematode C. elegans is the perfect model for studying this epigenetic phenomenon C. elegans are amenable to RNAi and RNAi induced silencing of genes in the germ line can be heritable for many (>10) generations. This thesis aims to better understand the mechanism and genetics of RNAi inheritance in the C. elegans germ line. Chapter 2 of this thesis presents the identification of a novel nuclear Ago that promotes germline RNAi inheritance. Chapter 2 also highlights the importance of nuclear silencing in multigenerational RNAi inheritance and suggests that heterochromatin and siRNAs might act as heritable agents of RNAi memory. RNAi inheritance does not last forever. Chapter 3 explores the idea that the reason RNAi inheritance does not last forever might be because it is under negative regulation. Chapter 3 presents preliminary results from a forward genetic screen that was conducted to identify mutants in which RNAi inheritance is no longer limited and RNAi silencing can essentially become permanent.