Chinese Journal of Magnetic Resonance ›› 2015, Vol. 32 ›› Issue (2): 318-328.doi: 10.11938/cjmr20150214

Previous Articles     Next Articles

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).

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

CLC Number: