波谱学杂志 ›› 2015, Vol. 32 ›› Issue (2): 318-328.doi: 10.11938/cjmr20150214

• 研究论文 • 上一篇    下一篇

Lin28 特异性结合let-7 RNA 结构基础

卢秀秀1§,顾嘉琦2§,蓝文贤1,王春喜1,麻锦彪2*,曹春阳1*   

  1. 1. 中国科学院 上海有机化学研究所, 生命有机化学国家重点实验室,上海 200032;
    2. 复旦大学 生命科学学院,遗传工程国家重点实验室,上海 200433
  • 收稿日期:2015-03-06 修回日期:2015-05-11 出版日期:2015-06-05 发布日期:2015-06-05
  • 作者简介:*通讯联系人:曹春阳,电话:+86-21-54925491;传真:+86-21-64166128; E-mail: ccao@mail.sioc.ac.cn;麻锦彪,电话:+86-21-51630542;传真:+86-21-51630541; E-mail: majb@fudan.edu.cn. §并列第一作者.
  • 基金资助:

    Grants from the Ministry of Science and Technology of China (2011CB966300), the National Natural Science Foundation of China (21272261, 21472229 and 21275154), and the Science and Technology Commission of Shanghai Municipality (15ZR1449300).

Structural Basis for Lin28 Specific Interaction with let-7 RNA

LU Xiu-xiu1§,GU Jia-qi2§,LAN Wen-xian1,WANG Chun-xi1,MA Jin-biao2*,CAO Chun-yang1*   

  1. 1. State Key Laboratory of Bio-Organic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032;
    2. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433
  • Received:2015-03-06 Revised:2015-05-11 Online:2015-06-05 Published:2015-06-05
  • About author:*Corresponding author: CAO Chun-yang, Tel: +86-21-54925491, Fax: +86-21-64166128, E-mail: ccao@mail. sioc.ac.cn; MA Jin-biao, Tel: +86-21-51630542, Fax: +86-21-51630541, E-mail: majb@fudan.edu.cn. §These authors contributed equally to this work.
  • Supported by:

    Grants from the Ministry of Science and Technology of China (2011CB966300), the National Natural Science Foundation of China (21272261, 21472229 and 21275154), and the Science and Technology Commission of Shanghai Municipality (15ZR1449300).

摘要:

let-7 miRNA 家族控制许多决定细胞命运的基因的表达,从而影响细胞的多能性、分化和转化.Lin28 是一个let-7 生物合成的转录后抑制因子,其碳端的锌指结构域特异性地结合一个保守的GGAG 或者一个类似GGAG 的let-7 miRNA 模块.作者报道了人源Lin28 与5′-A–2A–1G1G2A3G4-3′ let-7 RNA 复合物的核磁共振结构.Lin28 中两个Lin28 ZKD 识别了RNA 中的G1G2A3G4.复合物所有的碱基采取反式构象,RNA 的骨架因为Lin28 的结合变得弯曲,与之前报道的晶体结构一致而与NMR 结构不同,从而进一步确认了Lin28 识别RNA 的作用模式

关键词: let-7, Lin28, Zn-knuckle, 核磁共振, 结构

Abstract:

The let-7 miRNA (microRNA) family control many cell-fate determination genes to influence pluripotency, differentiation, and transformation. Lin28 is a specific, posttranscriptional inhibitor of let-7 biogenesis. The C-terminal Zn-knuckle domain (ZKD) of Lin28 specially interacts with a conserved GGAG or GGAG-like motif in let-7 miRNA. We here report the NMR structure of human Lin28 binding to let-7 RNA with a sequence of 5′-A–2A–1G1G2A3G4-3′,
demonstrating that the two folded domains of Lin28 ZKD recognize the region G1G2A3G4 of the RNA. All bases in bound RNA adopt anti conformation, and the backbone of RNA is bent due to Lin28 binding, consistent with the observations in the previous crystal structure, but different from those in the reported NMR structure, further confirming the structural basis for how Lin28 specially recognizes this RNA.

Key words: let-7, Lin28, Zn-knuckle, NMR, structure

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