Structural basis for the sequence-specific RNA-recognition mechanism of human CUG-BP1 RRM3.
Structural basis for the sequence-specific RNA-recognition mechanism of human CUG-BP1 RRM3.
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DOI：
10.1093/nar/gkp546
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发表时间：
2009-08
影响因子：
14.9
通讯作者：
Yokoyama S
中科院分区：
文献类型：
--
作者：
Tsuda K;Kuwasako K;Takahashi M;Someya T;Inoue M;Terada T;Kobayashi N;Shirouzu M;Kigawa T;Tanaka A;Sugano S;Güntert P;Muto Y;Yokoyama S
CUG结合蛋白1（CUG-BP 1）是CUG-BP 1和ETR样因子（CELF）家族或Bruno-like家族的成员，并且参与剪接、翻译和mRNA降解的控制。已经预测了CUG-BP 1的几个靶RNA序列，如CUG三联体重复序列、核前体mRNA和/或胞质mRNA的富含GU的序列和富含AU的元件。CUG-BP 1具有三个RNA识别基序（RRM），其中第三个RRM（RRM 3）可以单独与靶RNA结合。在这项研究中，我们解决了溶液结构的CUG-BP 1 RRM 3的异核NMR光谱。CUG-BP 1 RRM 3呈现非典型的RRM折叠，四链β折叠表面与N-末端延伸紧密结合。此外，我们确定了CUG-BP 1 RRM 3在与（UG）3 RNA的复合物中的溶液结构，并发现UGU三核苷酸通过β-折叠表面和N-末端延伸形成的口袋内的广泛堆叠相互作用和氢键被特异性识别。本研究揭示了CUG-BP 1 RRM 3能够区分短RNA片段与其他序列的独特机制，从而为理解RRM 3在CELF/Bruno-like家族中的作用提供了分子基础。
The CUG-binding protein 1 (CUG-BP1) is a member of the CUG-BP1 and ETR-like factors (CELF) family or the Bruno-like family and is involved in the control of splicing, translation and mRNA degradation. Several target RNA sequences of CUG-BP1 have been predicted, such as the CUG triplet repeat, the GU-rich sequences and the AU-rich element of nuclear pre-mRNAs and/or cytoplasmic mRNA. CUG-BP1 has three RNA-recognition motifs (RRMs), among which the third RRM (RRM3) can bind to the target RNAs on its own. In this study, we solved the solution structure of the CUG-BP1 RRM3 by hetero-nuclear NMR spectroscopy. The CUG-BP1 RRM3 exhibited a noncanonical RRM fold, with the four-stranded β-sheet surface tightly associated with the N-terminal extension. Furthermore, we determined the solution structure of the CUG-BP1 RRM3 in the complex with (UG)3 RNA, and discovered that the UGU trinucleotide is specifically recognized through extensive stacking interactions and hydrogen bonds within the pocket formed by the β-sheet surface and the N-terminal extension. This study revealed the unique mechanism that enables the CUG-BP1 RRM3 to discriminate the short RNA segment from other sequences, thus providing the molecular basis for the comprehension of the role of the RRM3s in the CELF/Bruno-like family.
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Pfam：氏族、网络工具和服务。
影响因子：
14.9
作者：
Finn, Robert D.;Mistry, Jaina;Schuster-Bockler, Benjamin;Griffiths-Jones, Sam;Hollich, Volker;Lassmann, Timo;Moxon, Simon;Marshall, Mhairi;Khanna, Ajay;Durbin, Richard;Eddy, Sean R.;Sonnhammer, Erik L. L.;Bateman, Alex
通讯作者：
Bateman, Alex
DOI：
10.1023/b:jsfg.0000029204.57846.7d
发表时间：
2004-01-01
期刊：
Journal of Structural and Functional Genomics
影响因子：
--
作者：
Kigawa, Takanori;Yabuki, Takashi;Yokoyama, Shigeyuki
通讯作者：
Yokoyama, Shigeyuki
影响因子：
13.8
作者：
Jeanmougin, F;Thompson, JD;Gibson, TJ
通讯作者：
Gibson, TJ
影响因子：
3
作者：
Duan, Y;Wu, C;Kollman, P
通讯作者：
Kollman, P
影响因子：
2.9
作者：
FARROW, NA;MUHANDIRAM, R;KAY, LE
通讯作者：
KAY, LE