Making sense of antisense: the activities of RNA-dependent RNA polymerases in endogenous RNAi

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In RNA-mediated interference (RNAi), small non-coding RNAs (siRNAs) are generated to direct specific gene silencing as they program a variety of effector complexes to degrade cognate messenger RNAs, or silence their transcription. Many RNAi-like pathways function endogenously in plants, fungi, yeast, and animals. Endogenous (endo)RNAi refers to mechanisms wherein siRNAs are derived from and converge back on endogenous loci. While the gene silencing steps of endoRNAi are becoming clear, little is known about their initiation, and on the basis of their specificity. RNA-dependent RNA polymerases (RdRP) are often central to initiation of endoRNAi. With this grant, we will examine the RRF-3 RdRP to decipher the basis for its specificity, and elucidate the mechanism of ERI endoRNAi initiation.