POLY(A)-BINDING PROTEIN-RNA COMPLEX

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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 多聚腺苷酸结合蛋白（Poly（A）-binding protein，PABP）是一种重要的调节蛋白，它同时控制mRNA的翻译和降解. PABP结合poly（A）RNA，并沿沿着poly（A）尾组织成未定义的寡聚化结构，该寡聚化结构以重复的27-nt模式保护mRNA免受核酸酶的侵害。PABP具有四个结合RNA的RRM基序。存在与7个腺苷酸复合的RRM 1 -2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。在C末端有一个小的球状结构域，其结构通过NMR解析，并且包含用于与翻译释放因子3（eRF 3）、PABP调节蛋白（PAIP 2）和多聚（A）核酸酶（Pan 3）相互作用的结合裂缝。C-末端结构域的其他不太明确的区域结合60 S核糖体、起始因子（eIF 4 B）、翻译刺激因子（Paip 1）和共济失调蛋白2。 长期目标是确定PABP与eIF 4G和eRF 3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的PABP部分的切割（由替代构象指导）如何能够关闭脊髓灰质炎病毒mRNA翻译并同时激活相同模板上的病毒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PCBP 2（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合成起始不是发生在poly（A）尾的3'端，而是发生在3'非翻译区的3'端的内部20个核苷酸处（3）。我们假设一个PABP被用作聚合酶放置在模板上的分子工具。然而，对于如何选择沿着poly（A）尾的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物，没有基本原理

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