POLY(A)-BINDING PROTEIN-RNA COMPLEX

多聚 (A) 结合蛋白-RNA 复合物

• 批准号: 8168604
• 负责人: Richard E Lloyd
• 金额: $ 1.08万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-15 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168604
• 关键词: 3' Untranslated Regions; Alanine; Binding; C-terminal; Cleaved cell; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA-Directed RNA Polymerase; Funding; Genetic Translation; Goals; Grant; Human poliovirus; Institution; Messenger RNA; Molecular; Molecular Conformation; Nucleotides; Pattern; Peptide Initiation Factors; Polioviruses; Poly A; Poly(A) Tail; Poly(A)+ RNA; Poly(A)-Binding Proteins; Poly(A)-specific ribonuclease; Polymerase; Proline; RNA Binding; RNA chemical synthesis; RNA replication; RNA-Binding Proteins; Recycling; Research; Research Personnel; Resources; Ribosomes; Source; Structure; Translation Initiation; Translations; United States National Institutes of Health; Viral; adenylate; eIF-4B; genetic regulatory protein; molecular marker; nuclease; release factor 3; tool; viral RNA

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. Poly(A)-binding protein (PABP) is a critical regulatory protein that simultaneously controls mRNA translation and decay. PABP binds poly(A) RNA and organizes into undefined oligomerized structures along poly(A) tails that protect mRNA from nucleases in a repeating 27-nt pattern. PABP has four RRM motifs that bind RNA. A structure exists for RRM1-2 complexed with 7 adenylates. The C-terminal domain is enigmatic. It is proline and alanine-rich and nearly half the molecule. There is a small globular domain at the extreme C-terminus whose structure was solved by NMR, and contains a binding cleft for interactions with translation release factor 3(eRF3), and PABP regulatory protein (PAIP2), and poly(A)nuclease (Pan3). Other less defined regions of the C-terminal domain bind 60S ribosomes, initiation factors (eIF4B), translation stimulatory factors (Paip1) and ataxin2. Long term goals are to determine how interactions of PABP with eIF4G and eRF3 regulate de novo translation initiation versus ribosome 3'-5' recycling. Another long term goal is to understand how cleavage of select PABP moieties (directed by alternate conformations), is able to shut off poliovirus mRNA translation and simultaneously activate viral RNA replication on the same template. This is known to involve 5' -3 interactions between viral 3CD (RNA polymerase precursor), PCBP2 (cellular RNA-binding protein) on the viral 5' cloverleaf structure and PABP on the poly(A) tail. Viral RNA synthesis initiation occurs not at the 3' end of the poly(A) tail, but internally, 20 nucleotides from the 3' end of the 3' untranslated region (3). We hypothesize that one PABP is used as a molecular tool for polymerase placement on the template. However, there is no rationale for how one of 3-4 potential PABP moieties along the poly(A) tail is chosen as a molecular marker for directed cleavage and polymerase access to the template

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 Poly(A) 结合蛋白 (PABP) 是一种关键的调节蛋白，可同时控制 mRNA 翻译和降解。 PABP 结合聚 (A) RNA 并沿着聚 (A) 尾组织成未定义的寡聚结构，以重复的 27-nt 模式保护 mRNA 免受核酸酶的侵害。 PABP 有四个结合 RNA 的 RRM 基序。 RRM1-2 存在与 7 个腺苷酸复合的结构。 C 末端结构域是神秘的。它富含脯氨酸和丙氨酸，几乎占分子的一半。最末端 C 末端有一个小球状结构域，其结构已通过 NMR 解析，并且包含一个用于与翻译释放因子 3 (eRF3)、PABP 调节蛋白 (PAIP2) 和聚 (A) 核酸酶 (Pan3) 相互作用的结合裂缝。 C 端结构域的其他不太明确的区域结合 60S 核糖体、起始因子 (eIF4B)、翻译刺激因子 (Paip1) 和 ataxin2。 长期目标是确定 PABP 与 eIF4G 和 eRF3 的相互作用如何调节从头翻译起始与核糖体 3'-5' 回收。另一个长期目标是了解选择性 PABP 部分（由替代构象指导）的裂解如何能够关闭脊髓灰质炎病毒 mRNA 翻译并同时激活同一模板上的病毒 RNA 复制。已知这涉及病毒 3CD（RNA 聚合酶前体）、病毒 5' 三叶草结构上的 PCBP2（细胞 RNA 结合蛋白）和 Poly(A) 尾上的 PABP 之间的 5' -3 相互作用。病毒 RNA 合成起始点并非发生在 Poly(A) 尾的 3' 末端，而是在内部，距 3' 非翻译区 3' 末端 20 个核苷酸处 (3)。我们假设一个 PABP 被用作将聚合酶放置在模板上的分子工具。然而，对于如何选择沿 Poly(A) 尾部的 3-4 个潜在 PABP 部分之一作为定向切割和聚合酶接近模板的分子标记，尚无任何理由。