Butcher Samuel E
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA.
Met Ions Life Sci. 2011;9:235-51. doi: 10.1039/9781849732512-00235.
The spliceosome is a massive complex of 5 RNAs and many proteins that associate to catalyze precursor messenger RNA splicing. The process of splicing involves two phosphoryl transfer reactions that result in intron excision and ligation of the flanking exons. Since it is required for normal protein production in eukaryotic cells, pre-mRNA splicing is an essential step in gene expression. Although high resolution structural views of the spliceosome do not yet exist, a growing body of evidence indicates that the spliceosome is a magnesium-dependent enzyme that utilizes catalytic metal ions to stabilize both transition states during the two phosphoryl transfer steps of splicing. A wealth of data also indicate that the core of the spliceosome is comprised of RNA, and suggest that the spliceosome may be a ribozyme. This chapter presents the evidence for metal ion catalysis by the spliceosome, draws comparisons to similar RNA enzymes, and discusses the future directions for research into the mechanism of pre-mRNA splicing.
剪接体是一个由5种RNA和许多蛋白质组成的庞大复合体,这些成分结合在一起催化前体信使RNA的剪接。剪接过程涉及两个磷酸转移反应,其结果是内含子被切除,侧翼外显子被连接。由于它是真核细胞正常蛋白质生产所必需的,前体mRNA剪接是基因表达中的一个关键步骤。尽管目前还没有剪接体的高分辨率结构视图,但越来越多的证据表明,剪接体是一种依赖镁的酶,它利用催化金属离子来稳定剪接过程中两个磷酸转移步骤的过渡态。大量数据还表明,剪接体的核心由RNA组成,并暗示剪接体可能是一种核酶。本章介绍了剪接体金属离子催化的证据,与类似的RNA酶进行了比较,并讨论了前体mRNA剪接机制研究的未来方向。
Met Ions Life Sci. 2011
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