RNA catalyses nuclear pre-mRNA splicing

摘要

In nuclear pre-messenger RNA splicing, introns are excised by the spliceosome, a dynamic machine composed of both proteins and small nuclear RNAs (snRNAs). Over thirty years ago, after the discovery of self-splicing group Ⅱ intron RNAs ， the snRNAs were proposed to catalyse splicing. However, no definitive evidence for a role of either RNA or protein in catalysis by the spliceosome has been reported so far. By using metal rescue strategies in spliceosomes from budding yeast, here we show that the U6 snRNA catalyses both of the two splicing reactions by positioning divalent metals that stabilize the leaving groups during each reaction. Notably, all of the U6 catalytic metal ligands we identified correspond to the ligands observed to position catalytic, divalent metals in crystal structures of a group Ⅱ intron RNA. These findings indicate that group Ⅱ introns and the spliceosome share common catalytic mechanisms and probably common evolutionary origins. Our results demonstrate that RNA mediates catalysis within the spliceosome.%含RNA和含蛋白的剪接体复合物能将内含子从 pre-mRNAs切除。在自剪接"group Ⅱ内含子"(一种核酶）存在的基础上，人们在30多年前假设，剪接体的"小核RNAs"(snRNAs)会催化剪接。然而，尽管经过了几十年的研究，此前仍未有关于RNA或蛋白在剪接催化中起某种作用的明确证据见诸报道。现在，Joseph Piccirilli及同事发现含金属的U6 snRNA是这种催化剂。而且，他们的数据也强有力地说明，剪接体和"groupⅡ内含子"有一个共同的演化起源。