Lin28特异性结合let-7 RNA结构基础

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．...

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Published in波谱学杂志 Vol. 32; no. 2; pp. 318 - 328
Main Author 卢秀秀 顾嘉琦 蓝文贤 王春喜 麻锦彪 曹春阳
Format Journal Article
LanguageChinese
Published 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%复旦大学生命科学学院，遗传工程国家重点实验室，上海 200433 2015
Subjects
let-7
Lin28
Zn—knuckle
核磁共振
结构
NMR
let-7
Lin28
Zn-knuckle
核磁共振
结构
structure
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Summary: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．
Bibliography: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.
LU Xiu-xiu, GU Jia-qi, LAN Wen-xian, WANG Chun-xi, MA Jin-biao, CAO Chun-yang （1. State Key Laboratory of Bio-Organic and Natural Product Chemistry, Shanghai Institute o
ISSN:1000-4556
DOI:10.11938/cjmr20150214