The role of the poly(A)-specific ribonuclease (PARN) in mRNA decay

poly（A）尾的降解（去腺苷酸化）是许多mRNA降解的第一步和限速步骤。脱腺苷酸化也被用作卵母细胞成熟和早期发育过程中的翻译控制手段。我们已经纯化并克隆了一种poly（A）特异性3 '-核糖核酸外切酶（PARN），它负责卵母细胞中的去腺苷酸化，也可能在体细胞中。令人惊讶的是，核酸酶偏好携带5'帽的底物RNA。目前的应用有三个目标：第一，在真核系统中过量生产足够数量的PARN，以允许表征酶的功能特性，特别是帽依赖性和持续合成能力;第二，mRNA翻译和衰变之间的关系的调查;和，第三，产生敲除小鼠，以获得关于PARN的生理作用的明确证据。

Degradation of the poly(A) tail (deadenylation) is the first and rate-limiting step in the decay of many mRNAs. Deadenylation is also used as a means of translational control during oocyte maturation and early development. We have purified and cloned a poly(A)-specific 3'-exoribonuclease (PARN) that is responsible for deadenylation in oocytes and possible also in somatic cells. Surprisingly, the nuclease prefers substrate RNAs carrying a 5' cap. The current application has three goals: First, overproduction of sufficient quantities of PARN in a eukaryotic system to allow a characterisation of the enzyme's functional properties, in particular cap dependence and processivity; second, the investigation of the relationship between mRNA translation and decay; and, third, the generation of a knock-out mouse to obtain definitive evidence regarding the physiological role of PARN.