Department of Chemistry & Biochemistry, University of California, San Diego, CA 92093-0356, USA.
Molecules. 2017 Jan 2;22(1):75. doi: 10.3390/molecules22010075.
Group I intron ribozymes occur naturally as -splicing ribozymes, in the form of introns that do not require the spliceosome for their removal. Instead, they catalyze two consecutive -phosphorylation reactions to remove themselves from a primary transcript, and join the two flanking exons. Designed, -splicing variants of these ribozymes replace the 3'-portion of a substrate with the ribozyme's 3'-exon, replace the 5'-portion with the ribozyme's 5'-exon, or insert/remove an internal sequence of the substrate. Two of these designs have been evolved experimentally in cells, leading to variants of group I intron ribozymes that splice more efficiently, recruit a cellular protein to modify the substrate's gene expression, or elucidate evolutionary pathways of ribozymes in cells. Some of the artificial, -splicing ribozymes are promising as tools in therapy, and as model systems for RNA evolution in cells. This review provides an overview of the different types of -splicing group I intron ribozymes that have been generated, and the experimental evolution systems that have been used to improve them.
I 类内含子核酶自然存在于 -剪接核酶中，形式为不需要剪接体就能被移除的内含子。相反，它们催化两个连续的 -磷酸化反应，从初级转录本中去除自身，并连接两个侧翼外显子。这些核酶的设计 -剪接变体用核酶的 3'-外显子替换底物的 3'-部分，用核酶的 5'-外显子替换 5'-部分，或插入/去除底物的内部序列。这两种设计已经在细胞中经过实验进化，导致 I 类内含子核酶的变体更有效地剪接，招募一种细胞蛋白来修饰底物的基因表达，或阐明细胞中核酶的进化途径。一些人工 -剪接核酶有望成为治疗工具，并作为细胞中 RNA 进化的模型系统。这篇综述概述了已经产生的不同类型的 -剪接 I 类内含子核酶，以及用于改进它们的实验进化系统。
