CAJ | 학술논문

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．
let-7 miRNA가족공제허다결정세포명운적기인적표체，종이영향세포적다능성、분화화전화．Lin28시일개let-7생물합성적전록후억제인자，기탄단적자지결구역특이성지결합일개보수적GGAG혹자일개유사GGAG적let-7 miRNA모괴．작자보도료인원Lin28여5′-A–2A–1G1G2A3G4-3′ let-7 RNA복합물적핵자공진결구．Lin28중량개Lin28 ZKD식별료RNA중적G1G2A3G4．복합물소유적감기채취반식구상，RNA적골가인위Lin28적결합변득만곡，여지전보도적정체결구일치이여NMR결구불동，종이진일보학인료Lin28식별RNA적작용모식．
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.