POST-TRANSLATIONAL PROTEIN MODIFICATION AND RNA PROCESSING AND DECAY

翻译后蛋白质修饰以及 RNA 加工和衰变

• 批准号: 8169220
• 负责人: CHRISTOPHER D. LIMA
• 金额: $ 3.14万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169220
• 关键词: Biochemical; Cell Cycle Progression; Cleaved cell; Complex; Computer Retrieval of Information on Scientific Projects Database; Diphosphates; Enzymes; Eukaryota; Funding; Grant; Guanine; Guanosine Triphosphate; Institution; Lysine; Messenger RNA; Methyltransferase; Modification; Oligonucleotides; Organism; Peptide Hydrolases; Positioning Attribute; Post-Translational Protein Processing; Process; RNA; RNA Polymerase II; RNA Processing; RNA triphosphatase; Reaction; Research; Research Personnel; Resources; Saccharomycetales; Signal Transduction; Small Ubiquitin-Related Modifier Proteins; Source; Stress Response Signaling; Structure; System; Ubiquitin; United States National Institutes of Health; Yeasts; base; cell growth; cofactor; guanylate; mRNA capping; mRNA guanylyltransferase; nucleocytoplasmic transport; protein degradation; protein function; tripolyphosphate

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. Structural studies of mRNA capping & SUMO protein modification. mRNA capping. Three catalytic steps are required in all eukaryotic organisms to properly cap the nascent mRNA chain. The 5' triphosphate (pppN) of the mRNA is cleaved by RNA triphosphatase at the ¿ position to produce a 5' diphosphate (ppN) mRNA molecule. The product of this reaction is substrate for RNA guanylyltransferase in a reaction that transfers GMP from GTP to the 5' diphosphate end of the RNA producing GpppN. The cap guanylate is then methylated by RNA (guanine-7) methyltransferase to form the functional m7GpppN structure. Each of the cap- forming activities is essential for cell growth in budding yeast. We are characterizing the structural basis for several of these enzymes in complex with each other, in complex with various RNA and oligonucleotide compounds, and in complex with the phosphorylated CTD from RNA polymerase II. SUMO. The small ubiquitin-like modifier SUMO is known to regulate 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 appear to 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 several components of this system, both alone and in complex with each other. We are currently characterizing the structural basis for additional complexes between E1, E2, E3, SUMO and various substrates and cofactors.

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。子项目和 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所在的机构。 mRNA加帽和SUMO蛋白修饰的结构研究。mRNA加帽。 在所有真核生物中，需要三个催化步骤来适当地给新生mRNA链加帽。mRNA的5'三磷酸（pppN）被RNA三磷酸酶在？位置切割，产生5'二磷酸（ppN）mRNA分子。在将GMP从GTP转移到产生GpppN的RNA的5'二磷酸末端的反应中，该反应的产物是RNA鸟苷酰转移酶的底物。帽鸟苷酸然后被RNA（鸟嘌呤-7）甲基转移酶甲基化以形成功能性m7 GpppN结构。每一个帽形成活动是必不可少的芽殖酵母细胞生长。我们正在表征这些酶中的几种相互复合、与各种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复合的结构基础。相扑。已知小泛素样修饰物SUMO调节真核生物中的核转运、应激反应和信号转导，这是酵母中细胞周期进展所必需的过程。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修饰似乎并不靶向降解蛋白，而是通过细胞定位、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功能。我们已经在结构上描述了这个系统的几个组成部分，无论是单独的还是相互复杂的。我们目前正在表征E1，E2，E3，SUMO和各种底物和辅因子之间的其他复合物的结构基础。