Ding Zhan, Meng Yan-Ran, Fan Yu-Jie, Xu Yong-Zhen
RNA Institute, State Key Laboratory of Virology, and Hubei Key Laboratory of Cell Homeostasis, College of Life Science, Wuhan University, Wuhan, Hubei, China.
Key Laboratory of Insect Developmental and Evolutionary Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, China.
Wiley Interdiscip Rev RNA. 2023 Jan;14(1):e1761. doi: 10.1002/wrna.1761. Epub 2022 Sep 2.
Catalyzed by spliceosomes in the nucleus, RNA splicing removes intronic sequences from precursor RNAs in eukaryotes to generate mature RNA, which also significantly increases proteome complexity and fine-tunes gene expression. Most metazoans have two coexisting spliceosomes; the major spliceosome, which removes >99.5% of introns, and the minor spliceosome, which removes far fewer introns (only 770 at present have been predicted in the human genome). Both spliceosomes are large and dynamic machineries, each consisting of five small nuclear RNAs (snRNAs) and more than 100 proteins. However, the dynamic assembly, catalysis, and protein composition of the minor spliceosome are still poorly understood. With different splicing signals, minor introns are rare and usually distributed alone and flanked by major introns in genes, raising questions of how they are recognized by the minor spliceosome and how their processing deals with the splicing of neighboring major introns. Due to large numbers of introns and close similarities between the two machinery, cooperative, and competitive recognition by the two spliceosomes has been investigated. Functionally, many minor-intron-containing genes are evolutionarily conserved and essential. Mutations in the minor spliceosome exhibit a variety of developmental defects in plants and animals and are linked to numerous human diseases. Here, we review recent progress in the understanding of minor splicing, compare currently known components of the two spliceosomes, survey minor introns in a wide range of organisms, discuss cooperation and competition of the two spliceosomes in splicing of minor-intron-containing genes, and contributions of minor splicing mutations in development and diseases. This article is categorized under: RNA Processing > Processing of Small RNAs RNA Processing > Splicing Mechanisms RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry.
在细胞核中剪接体的催化下，RNA剪接从真核生物的前体RNA中去除内含子序列，以生成成熟RNA，这也显著增加了蛋白质组的复杂性并微调基因表达。大多数后生动物有两种共存的剪接体；主要剪接体去除超过99.5%的内含子，次要剪接体去除的内含子要少得多（目前人类基因组中仅预测到770个）。两种剪接体都是大型动态机器，每种都由五个小核RNA（snRNA）和100多种蛋白质组成。然而，次要剪接体的动态组装、催化和蛋白质组成仍知之甚少。由于不同的剪接信号，次要内含子很少见，通常单独分布，并在基因中被主要内含子侧翼包围，这就引发了它们如何被次要剪接体识别以及它们的加工如何处理相邻主要内含子剪接的问题。由于内含子数量众多且两种机制之间非常相似，因此对两种剪接体的协同和竞争性识别进行了研究。在功能上，许多含有次要内含子的基因在进化上是保守且必不可少的。次要剪接体中的突变在植物和动物中表现出各种发育缺陷，并与许多人类疾病有关。在这里，我们综述了对次要剪接理解的最新进展，比较了目前已知的两种剪接体的组成部分，调查了广泛生物体中的次要内含子，讨论了两种剪接体在含次要内含子基因剪接中的合作与竞争，以及次要剪接突变在发育和疾病中的作用。本文分类如下：RNA加工>小RNA加工；RNA加工>剪接机制；RNA结构与动力学>RNA结构、动力学和化学。
