The Ribonucleases Involved in RNA Interference

Dicer是一种核酸酶，参与将双链RNA（dsRNA）加工成小分子RNA。 siRNA和miRNA。这些小RNA参与调节 在包括人类在内的各种生物体中，许多基因的表达。该提案 将集中在切粒机的方面，在很大程度上是不确定的，如其功能， 解旋酶结构域及其在内源性siRNA（endo-siRNA）沉默中作用。突变 将被引入Dicer的解旋酶结构域，并使用 模式生物C. elegans，并在体外使用生化技术。的 将检验Dicer解旋酶结构域允许其前向功能的假设。 该实验室最近的研究结果表明，在解旋酶结构域发生突变的动物 缺乏某些内siRNA并积累它们的前体。后者将允许 第一次鉴定内siRNA前体。拟议的研究将推进 我们对切丁酶的理解，一种对生命至关重要的酶。

Dicer is a nuclease involved in processing double-stranded RNA (dsRNA) into small RNAs called siRNA and miRNA. These small RNAs are involved in regulating the expression of numerous genes, in diverse organisms, including humans. The proposal will focus on aspects of Dicer that are largely undefined, such as the function of its helicase domain and its role in silencing by endogenous siRNA (endo-siRNA). Mutations will be introduced into the helicase domain of Dicer, and effects monitored in vivo using the model organism C. elegans, and in vitro using biochemical techniques. The hypothesis that Dicer's helicase domain allows it to function processively will be tested. The laboratory's recent results indicate animals with mutations in the helicase domain are devoid of certain endo-siRNA and accumulate their precursors. The latter will allow the first characterization of endo-siRNA precursors. The proposed research will advance our understanding of Dicer, an enzyme that is absolutely essential for life.