Lin28 特异性结合let-7 RNA 结构基础
收稿日期: 2015-03-06
修回日期: 2015-05-11
网络出版日期: 2015-06-05
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
Received date: 2015-03-06
Revised date: 2015-05-11
Online published: 2015-06-05
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).
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
卢秀秀1§ , 顾嘉琦2§ , 蓝文贤1 , 王春喜1 , 麻锦彪2* , 曹春阳1* . Lin28 特异性结合let-7 RNA 结构基础[J]. 波谱学杂志, 2015 , 32(2) : 318 -328 . DOI: 10.11938/cjmr20150214
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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