Structural basis of pre-let-7 miRNA recognition by the zinc knuckles of pluripotency factor Lin28

被引：108
作者：
Loughlin, Fionna E. [2 ]
Gebert, Luca F. R. [1 ]
Towbin, Harry [1 ]
Brunschweiger, Andreas [1 ]
Hall, Jonathan [1 ]
Allain, Frederic H-T [2 ]
机构：
[1] ETH, Inst Pharmaceut Sci, Zurich, Switzerland
[2] ETH, Inst Mol Biol & Biophys, Zurich, Switzerland
来源：
NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2012年 / 19卷 / 01期
基金：
瑞士国家科学基金会;
关键词：
HIV-1 NUCLEOCAPSID PROTEIN; NMR STRUCTURE; MICRORNA BIOGENESIS; LET-7; MICRORNA; RNA; LIN-28; MATURATION; ASSIGNMENT; FINGER; GENOME;
D O I：
10.1038/nsmb.2202
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Lin28 inhibits the biogenesis of let-7 miRNAs through a direct interaction with the terminal loop of pre-let-7. This interaction requires the zinc-knuckle domains of Lin28. We show that the zinc knuckle domains of Lin28 are sufficient to provide binding selectivity for pre-let-7 miRNAs and present the NMR structure of human Lin28 zinc knuckles bound to the short sequence 5'-AGGAGAU-3'. The structure reveals that each zinc knuckle recognizes an AG dinucleotide separated by a single nucleotide spacer. This defines a new 5'-NGNNG-3' consensus motif that explains how Lin28 selectively recognizes pre-let-7 family members. Binding assays in cell lysates and functional assays in cultured cells demonstrate that the interactions observed in the solution structure also occur between the full-length protein and members of the pre-let-7 family. The consensus sequence explains several seemingly disparate previously published observations on the binding properties of Lin28.
引用
收藏
页码：84 / U105
页数：8
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