Wu J A, Manley J L
Department of Biological Sciences, Columbia University, New York, New York 10027.
Nature. 1991 Aug 29;352(6338):818-21. doi: 10.1038/352818a0.
Splicing of pre-messenger RNA in eukaryotic cells occurs in a multicomponent complex termed the spliceosome, which contains small nuclear ribonucleoprotein particles (snRNPs), protein factors and substrate pre-mRNA. Assembly of the spliceosome involves the stepwise binding of snRNPs and protein factors to the pre-mRNA through a poorly understood mechanism which probably involves specific RNA-RNA, RNA-protein and protein-protein interactions. Of particular interest are the interactions between snRNPs, which are likely to be important not only for assembly of the spliceosome but also for catalysis. U1 snRNP interacts with the 5' splice site and U2 snRNP with the branch site of the pre-mRNA; both of these interactions involve Watson-Crick base pairing. But very little is known about how other factors such as the U4/U6 and U5 snRNPs reach the spliceosome and function in splicing. Here we report evidence that U6 snRNA interacts directly with U2 snRNA by a mechanism involving base-pairing, and that this interaction can be necessary for splicing of a mammalian pre-mRNA in vivo.
真核细胞中前体信使RNA的剪接发生在一个称为剪接体的多组分复合物中，该复合物包含小核核糖核蛋白颗粒（snRNP）、蛋白质因子和底物前体mRNA。剪接体的组装涉及snRNP和蛋白质因子通过一种尚未完全了解的机制逐步与前体mRNA结合，这一机制可能涉及特定的RNA-RNA、RNA-蛋白质和蛋白质-蛋白质相互作用。特别令人感兴趣的是snRNP之间的相互作用，这可能不仅对剪接体的组装很重要，而且对催化也很重要。U1 snRNP与前体mRNA的5'剪接位点相互作用，U2 snRNP与前体mRNA的分支位点相互作用；这两种相互作用都涉及沃森-克里克碱基配对。但是对于其他因子，如U4/U6和U5 snRNP如何到达剪接体并在剪接中发挥作用，人们了解得很少。在这里，我们报告证据表明，U6 snRNA通过一种涉及碱基配对的机制直接与U2 snRNA相互作用，并且这种相互作用对于体内哺乳动物前体mRNA的剪接可能是必要的。
