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

在RNA介导的干扰(RNAi)中，小的非编码RNA(SiRNAs)被产生来指导特定的基因沉默，因为它们编程各种效应复合体来降解同源信使RNA或沉默它们的转录。许多类似RNAi的途径在植物、真菌、酵母和动物中发挥内源性作用。内源(Endo)RNAi是指siRNAs来源于内源基因并汇聚回内源基因的机制。虽然EndoRNAi的基因沉默步骤变得越来越清楚，但人们对它们的启动以及基于它们的特异性知之甚少。依赖于RNA的RNA聚合酶(RdRP)通常是内源RNAi启动的中心。有了这笔赠款，我们将研究RRF-3RdRP，以破译其特异性的基础，并阐明ERI EndoRNAi启动的机制。

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.