Recognition of RNA polymerase II carboxy-terminal domain by 3′-RNA-processing factors
Recognition of RNA polymerase II carboxy-terminal domain by 3′-RNA-processing factors
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DOI：
10.1038/nature02679
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发表时间：
2004-07-08
期刊：
影响因子：
64.8
通讯作者：
Cramer, P
中科院分区：
文献类型：
--
作者：
Meinhart, A;Cramer, P
在转录过程中，RNA聚合酶（Pol）II合成真核生物信使RNA。转录通过Pol II的羧基末端结构域（CTD）与RNA加工偶联，该结构域由序列Tyr 1-Ser 2-Pro 3-Thr 4-Ser 5-Pro 6-Ser 7的多达52个重复组成（参考文献1，2）。磷酸化后，CTD与蛋白Pcf 11和Nrd 1中的保守CTD相互作用结构域（CID）紧密结合，Pcf 11和Nrd 1分别是多聚腺苷酸化依赖性和非依赖性3 '-RNA加工的必需和进化保守因子。在这里，我们描述的结构的Ser 2-磷酸化CTD肽结合的CID结构域的Pcf 11。CTD基序Ser 2-Pro 3-Thr 4-Ser 5形成结合CID结构域中保守沟的β转角。Ser 2磷酸基团不与CID结构域直接接触，但可以间接识别，因为它通过额外的氢键稳定β-转角。肽结构的迭代导致CTD的紧凑β-螺旋模型。该模型表明，在mRNA的转录加工周期中，CTD中的紧凑螺旋区域以磷酸化依赖的方式被解开和再生。
During transcription, RNA polymerase (Pol) II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing by the carboxy-terminal domain (CTD) of Pol II, which consists of up to 52 repeats of the sequence Tyr1-Ser 2-Pro 3-Thr 4-Ser 5-Pro 6-Ser 7 (refs 1, 2). After phosphorylation, the CTD binds tightly to a conserved CTD-interacting domain ( CID) present in the proteins Pcf11 and Nrd1, which are essential and evolutionarily conserved factors for polyadenylation-dependent and -independent 3'-RNA processing, respectively. Here we describe the structure of a Ser 2-phosphorylated CTD peptide bound to the CID domain of Pcf11. The CTD motif Ser 2-Pro 3-Thr 4-Ser 5 forms a beta-turn that binds to a conserved groove in the CID domain. The Ser 2 phosphate group does not make direct contact with the CID domain, but may be recognized indirectly because it stabilizes the beta-turn with an additional hydrogen bond. Iteration of the peptide structure results in a compact beta-spiral model of the CTD. The model suggests that, during the mRNA transcription-processing cycle, compact spiral regions in the CTD are unravelled and regenerated in a phosphorylation-dependent manner.