STRUCTURAL STUDIES OF MRNA METABOLISM & SUMO PROTEIN MODIFICATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 相扑。小的泛素样修饰物SUMO调节真核生物的核运输、应激反应和信号转导，这一过程对酵母的细胞周期进程至关重要。与泛素修饰类似，相扑结合发生在赖氨酸残基上，并由相扑激活酶E1、相扑结合酶E2、相扑结合酶、E3样结合辅因子以及催化相扑加工和去共轭的蛋白酶催化。相扑修饰通常不以蛋白质为降解目标，而是通过改变细胞定位、生化激活或通过保护泛素依赖的降解来改变目标蛋白质的功能。我们有这个系统的结构特征组件，既有单独的，也有与底物和辅助因子组成的复杂的。我们正在继续努力表征E1、E2、E3、相扑与各种底物和辅因子之间其他络合物的结构基础。 信使核糖核酸成熟和衰退。细胞内信使核糖核酸的稳定性和寿命取决于前信使核糖核酸的加工和衰变途径。我们研究了与RNA封顶相关的早期加工事件，包括真核生物封顶新生mRNA链所需的催化步骤。每一种帽子形成活动对细胞生长都是必不可少的，我们正在鉴定其中几种酶的结构基础，这些酶相互复合，与RNA和寡核苷酸化合物复合，以及与来自RNA聚合酶II的磷酸化CTD复合。RNA衰变在RNA代谢中也起着重要作用，我们从事的研究旨在阐明真核外体催化3‘-5’衰变的调节机制。真核外体是一种大的多亚单位复合体，包含催化进行性和/或分布性3‘-5’外切核酸酶活性的亚基。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SUMO. The small ubiquitin-like modifier SUMO regulates nuclear transport, stress response, and signal transduction in eukaryotes, a process that is essential for cell cycle progression in yeast. Analogous to ubiquitin modification, SUMO conjugation occurs on lysine residues and is catalyzed by E1, the SUMO activating enzyme, E2, the SUMO conjugation enzyme, E3-like conjugation cofactors, and proteases that catalyze SUMO processing and deconjugation. SUMO modification does not typically target proteins for degradation, but rather alters the target protein function through changes in cellular localization, biochemical activation, or through protection from ubiquitin-dependent degradation. We have structurally characterized components of this system, both alone and in complex with substrates and co-factors. We are continuing efforts to characterize the structural basis for additional complexes between E1, E2, E3, SUMO with various substrates and cofactors. mRNA maturation and decay. The stability and lifetime of cellular mRNA depends on pre-mRNA processing and decay pathways. We study early processing events associated with RNA capping including the catalytic steps that are required in eukaryotic organisms to cap the nascent mRNA chain. Each of the cap-forming activities is essential for cell growth and we are characterizing the structural basis for several of these enzymes in complex with each other, in complex with RNA and oligonucleotide compounds, and in complex with phosphorylated CTD from RNA polymerase II. RNA decay also plays an important role in RNA metabolism, and we are engaged in studies aimed at elucidating regulatory mechanisms that regulate 3'-5' decay as catalyzed by the eukaryotic exosome, a large multi-subunit complex that contains subunits that catalyze processive and/or distributive 3'-5' exoribonuclease activities.