Wachtel Chaim, Manley James L
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, 52900 Ramat-Gan, Israel.
Mol Biosyst. 2009 Apr;5(4):311-6. doi: 10.1039/b820828j. Epub 2009 Jan 26.
Splicing of mRNA precursors was discovered over 30 years ago. It is one of the most complex steps in gene expression and therefore must be tightly controlled to ensure that splicing occurs efficiently and accurately. Splicing takes place in a large complex, the spliceosome, which contains approximately 200 proteins and five small RNAs (U snRNAs). Since its discovery, much work has been done to elucidate the pathway of the chemical reaction as well as the proteins and RNAs involved in catalysis. A variety of studies have established the potential for U2 and U6 snRNAs to play a role in splicing catalysis, raising the possibility that the spliceosome is a ribozyme. If correct, this would point to the spliceosomal proteins playing a supporting role during splicing. On the other hand, it may be that proteins contribute more directly to the spliceosomal active site, with the highly evolutionarily conserved Prp8 protein being an excellent candidate. This review will concentrate on recent work on splicing catalysis, and on elucidating the possible roles proteins play in this process.
mRNA前体的剪接在30多年前就被发现了。它是基因表达中最复杂的步骤之一,因此必须受到严格控制,以确保剪接高效且准确地发生。剪接发生在一个大型复合体——剪接体中,剪接体包含大约200种蛋白质和五种小RNA(U snRNA)。自发现以来,人们开展了大量工作来阐明化学反应途径以及参与催化的蛋白质和RNA。各种研究已经证实U2和U6 snRNA在剪接催化中发挥作用的可能性,这增加了剪接体是一种核酶的可能性。如果这是正确的,那么这将表明剪接体蛋白质在剪接过程中起辅助作用。另一方面,可能蛋白质对剪接体活性位点的贡献更为直接,高度进化保守的Prp8蛋白就是一个很好的候选者。本综述将集中于剪接催化的近期工作,以及阐明蛋白质在这一过程中可能发挥的作用。