Zhang Chaolin, Hastings Michelle L, Krainer Adrian R, Zhang Michael Q
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15028-33. doi: 10.1073/pnas.0703773104. Epub 2007 Sep 11.
As a result of large-scale sequencing projects and recent splicing-microarray studies, estimates of mammalian genes expressing multiple transcripts continue to increase. This expansion of transcript information makes it possible to better characterize alternative splicing events and gain insights into splicing mechanisms and regulation. Here, we describe a class of splice sites that we call dual-specificity splice sites, which we identified through genome-wide, high-quality alignment of mRNA/EST and genome sequences and experimentally verified by RT-PCR. These splice sites can be alternatively recognized as either 5' or 3' splice sites, and the dual splicing is conceptually similar to a pair of mutually exclusive exons separated by a zero-length intron. The dual-splice-site sequences are essentially a composite of canonical 5' and 3' splice-site consensus sequences, with a CAG|GURAG core. The relative use of a dual site as a 5' or 3' splice site can be accurately predicted by assuming competition for specific binding between spliceosomal components involved in recognition of 5' and 3' splice sites, respectively. Dual-specificity splice sites exist in human and mouse, and possibly in other vertebrate species, although most sites are not conserved, suggesting that their origin is recent. We discuss the implications of this unusual splicing pattern for the diverse mechanisms of exon recognition and for gene evolution.
由于大规模测序项目以及近期的剪接微阵列研究，对表达多种转录本的哺乳动物基因的估计持续增加。转录本信息的这种扩展使得更好地表征可变剪接事件并深入了解剪接机制和调控成为可能。在这里，我们描述了一类我们称为双特异性剪接位点的剪接位点，我们通过mRNA/EST与基因组序列的全基因组、高质量比对鉴定出这些位点，并通过RT-PCR进行了实验验证。这些剪接位点可以被交替识别为5'或3'剪接位点，并且双剪接在概念上类似于由零长度内含子分隔的一对互斥外显子。双剪接位点序列本质上是典型5'和3'剪接位点共有序列的复合体，具有CAG|GURAG核心。通过假设分别参与识别5'和3'剪接位点的剪接体成分之间对特异性结合的竞争，可以准确预测双位点作为5'或3'剪接位点的相对使用情况。双特异性剪接位点存在于人和小鼠中，可能也存在于其他脊椎动物物种中，尽管大多数位点并不保守，这表明它们是近期起源的。我们讨论了这种不寻常的剪接模式对外显子识别的多种机制以及基因进化的影响。
