snRNP公司
RNA剪接
小核RNA
内含子
小核核糖核蛋白
核糖核酸
核糖核蛋白
剪接体
RNA结合蛋白
细胞生物学
剪接
生物
剪接位点突变
结合位点
外显子
化学
遗传学
非编码RNA
基因
作者
Yasumasa Kondo,Chris Oubridge,Anne‐Marie M. van Roon,Kiyoshi Nagai
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2015-01-02
卷期号:4
被引量:202
摘要
U1 snRNP binds to the 5' exon-intron junction of pre-mRNA and thus plays a crucial role at an early stage of pre-mRNA splicing. We present two crystal structures of engineered U1 sub-structures, which together reveal at atomic resolution an almost complete network of protein-protein and RNA-protein interactions within U1 snRNP, and show how the 5' splice site of pre-mRNA is recognised by U1 snRNP. The zinc-finger of U1-C interacts with the duplex between pre-mRNA and the 5'-end of U1 snRNA. The binding of the RNA duplex is stabilized by hydrogen bonds and electrostatic interactions between U1-C and the RNA backbone around the splice junction but U1-C makes no base-specific contacts with pre-mRNA. The structure, together with RNA binding assays, shows that the selection of 5'-splice site nucleotides by U1 snRNP is achieved predominantly through basepairing with U1 snRNA whilst U1-C fine-tunes relative affinities of mismatched 5'-splice sites.
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