STRUCTURAL STUDIES OF MRNA METABOLISM & SUMO PROTEIN MODIFICATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 相扑。 SUMO调节真核生物的核转运、应激反应和信号转导，这是酵母细胞周期进程中必不可少的过程。与泛素修饰类似，SUMO缀合发生在赖氨酸残基上，并由E1（SUMO活化酶）、E2（SUMO缀合酶）、E3样缀合辅因子和催化SUMO加工和解缀合的蛋白酶催化。 SUMO修饰通常不靶向蛋白质进行降解，而是通过改变细胞定位、生物化学活化或通过保护免受泛素依赖性降解来改变靶蛋白质功能。我们已经在结构上表征了该系统的组成部分，无论是单独的还是与底物和辅因子的复合物。我们正在继续努力表征E1，E2，E3，SUMO与各种底物和辅因子之间的其他复合物的结构基础。 mRNA的成熟和衰变。细胞mRNA的稳定性和寿命取决于前mRNA的加工和衰变途径。我们研究了与RNA加帽相关的早期加工事件，包括真核生物中为新生mRNA链加帽所需的催化步骤。 每个帽形成活动是必不可少的细胞生长，我们正在表征的结构基础，这些酶中的几个相互复合，在复杂的RNA和寡核苷酸化合物，并在复杂的磷酸化CTD从RNA聚合酶II。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调节真核外泌体催化的3 '-5'衰变的调节机制，外泌体是一种大型多亚基复合物，含有催化进行性和/或分布性3 '-5'核糖核酸外切酶活性的亚基。

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.