The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex
The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex
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DOI：
10.1038/nsmb.2242
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发表时间：
2012-04-01
影响因子：
16.8
通讯作者：
Conti, Elena
中科院分区：
文献类型：
--
作者：
Murachelli, Andrea Giovanni;Ebert, Judith;Conti, Elena
ASAP复合物与外显子连接复合物（EJC）相互作用，EJC是一种参与转录后调控的信使核糖核蛋白复合物。三个ASAP亚基（Acinus、RNPS 1和SAP 18）已分别涉及转录调节、前mRNA剪接和mRNA质量控制。为了阐明ASAP与EJC相互作用的基础和后果，我们已经确定了真核ASAP核心复合物的1.9埃分辨率结构。RNPS 1的RNA识别基序与腺泡的保守基序结合，其识别模式与剪接U2 AF蛋白中观察到的识别模式相似。Acinus-RNPS 1平台招募SAP 18的泛素样结构域，形成具有RNA和蛋白质结合特性的三元复合物。出乎意料的是，我们的结构分析确定了一个Acinus样基序Pinin，另一个EJC相关的剪接因子。我们表明，Pinin物理相互作用RNPS 1和SAP 18，形成一个替代的三元复合物，PSAP。
The ASAP complex interacts with the exon-junction complex (EJC), a messenger ribonucleoprotein complex involved in post-transcriptional regulation. The three ASAP subunits (Acinus, RNPS1 and SAP18) have been individually implicated in transcriptional regulation, pre-mRNA splicing and mRNA quality control. To shed light on the basis for and consequences of ASAP's interaction with the EJC, we have determined the 1.9-angstrom resolution structure of a eukaryotic ASAP core complex. The RNA-recognition motif of RNPS1 binds to a conserved motif of Acinus with a recognition mode similar to that observed in splicing U2AF proteins. The Acinus-RNPS1 platform recruits the ubiquitin-like domain of SAP18, forming a ternary complex that has both RNA- and protein-binding properties. Unexpectedly, our structural analysis identified an Acinus-like motif in Pinin, another EJC-associated splicing factor. We show that Pinin physically interacts with RNPS1 and SAP18, forming an alternative ternary complex, PSAP.