Structural study of the disease-related splicing regulatory factors

疾病相关剪接调控因子的结构研究

• 批准号: 23370080
• 负责人: MUTO Yutaka
• 金额: $ 6.99万
• 依托单位: Musashino University (2013)The Institute of Physical and Chemical Research (2011-2012)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-11-18 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23370080/
• 关键词: 選択的スプライシング; 構造生物学; NMR; 制御因子; スプライシング; 前頭側頭型痴呆症; RNA結合蛋白質; Tra2β; ＮＭＲ; 超遠心分析; ＩＴＣ; helicase; ITC; SF2; SFM

Splicing reactions plays an important role in the regulation of the biological system. For the elucidation of its regulatory mechanism, the DNA sequence information is not enough and the structural information for the related splicing regulatory factors is necessary. First, in the present study, structural basis for the intermolecular coordination between multi splicing factors is investigated. Here we determined solution structure of a ternary complex composed of the RNA recognition motif (RRM) domains from an RBFOX family protein ASD-1 and a SUP-12-RBM24-RBM38 family member SUP-12 for the alternative splicing of the sole FGFR gene egl-15.The two RRM domains cooperatively interact with the RNA by sandwiching a guanine base to form the stable complex. In addition, investigation of the Tra2-b splicing factor and the target RNA revealed that the ternary and secondary structure of the target RNA affect the binding specificity to the corresponding splicing regulatory factors.

剪接反应在生物系统的调节中起着重要的作用。要阐明其调控机制，仅凭DNA序列信息是不够的，还需要相关剪接调控因子的结构信息。首先，在本研究中，多剪接因子之间的分子间协调的结构基础进行了研究。本文测定了RBFOX家族蛋白ASD-1和RBM 24-RBM 38家族成员ASD-12的RNA识别基序（RRM）结构域组成的三元复合物的溶液结构，这两个RRM结构域与RNA相互作用形成稳定的复合物。此外，对Tra 2-B剪接因子和靶RNA的研究表明，靶RNA的三级和二级结构影响与相应剪接调节因子的结合特异性。

项目成果

Structural basis for the dual RNA-recognition modes of human Tra2-・RRM

人类Tra2-・RRM双RNA识别模式的结构基础

• 发表时间: 2011
• 期刊: Nucleic Acids Res
• 影响因子: 14.9
• 作者: Tsuda;K.;Someya T.;Kuwasako K.;Takahashi M.;He F.;Unzai S.;Inoue M.;Harada T.;Watanabe S.;Terada T.;Kobayashi N.;Shirouzu M.;Kigawa T.;Tanaka A.;Sugano S.;Güntert P.;Yokoyama S. and Muto Y.
• 通讯作者: Yokoyama S. and Muto Y.

Structures of the first and second double-stranded RNA-binding domains of human TAR RNA-binding protein

• DOI: 10.1002/pro.543
• 发表时间: 2011-01-01
• 期刊: PROTEIN SCIENCE
• 影响因子: 8
• 作者: Yamashita, Seisuke;Nagata, Takashi;Yokoyama, Shigeyuki
• 通讯作者: Yokoyama, Shigeyuki

Structural insight into the interaction of ADP-ribose with the PARP WWE domains

• DOI: 10.1016/j.febslet.2012.09.009
• 发表时间: 2012-11-02
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: He, Fahu;Tsuda, Kengo;Muto, Yutaka
• 通讯作者: Muto, Yutaka

PARP11 WWEドメインによるADP-リボース認識機構の解明

PARP11 WWE 结构域对 ADP-核糖识别机制的阐明

• 作者: Fuhu He;津田健吾;高橋真梨;桑迫香奈子;寺田貴帆;白水美香子;渡部暁;木川隆則;小林直宏;PeterGüntert;横山茂之;武藤裕
• 通讯作者: 武藤裕

1H, 13C, and 15N resonance assignments of the dsRBDs of mouse RNA helicase A

小鼠 RNA 解旋酶 A dsRBD 的 1H、13C 和 15N 共振分配

• DOI: 10.1007/s12104-012-9380-3
• 发表时间: 2013
• 期刊: Biomolecular NMR Assignment
• 作者: Takashi Nagata T;Kengo Tsuda;Naohiro Kobayashi;Peter Guntert;Shigeyuki Yokoyama;and Yutaka Muto
• 通讯作者: and Yutaka Muto