Zheng Zhi-Ming
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
J Biomed Sci. 2004 May-Jun;11(3):278-94. doi: 10.1007/BF02254432.
Intron removal from a pre-mRNA by RNA splicing was once thought to be controlled mainly by intron splicing signals. However, viral and other eukaryotic RNA exon sequences have recently been found to regulate RNA splicing, polyadenylation, export, and nonsense-mediated RNA decay in addition to their coding function. Regulation of alternative RNA splicing by exon sequences is largely attributable to the presence of two major cis-acting elements in the regulated exons, the exonic splicing enhancer (ESE) and the suppressor or silencer (ESS). Two types of ESEs have been verified from more than 50 genes or exons: purine-rich ESEs, which are the more common, and non-purine-rich ESEs. In contrast, the sequences of ESSs identified in approximately 20 genes or exons are highly diverse and show little similarity to each other. Through interactions with cellular splicing factors, an ESE or ESS determines whether or not a regulated splice site, usually an upstream 3' splice site, will be used for RNA splicing. However, how these elements function precisely in selecting a regulated splice site is only partially understood. The balance between positive and negative regulation of splice site selection likely depends on the cis-element's identity and changes in cellular splicing factors under physiological or pathological conditions.
曾经认为，通过RNA剪接从pre-mRNA中去除内含子主要受内含子剪接信号控制。然而，最近发现病毒和其他真核RNA外显子序列除了其编码功能外，还能调节RNA剪接、聚腺苷酸化、输出以及无义介导的RNA降解。外显子序列对可变RNA剪接的调节很大程度上归因于受调节外显子中存在的两个主要顺式作用元件，即外显子剪接增强子（ESE）和抑制子或沉默子（ESS）。已从50多个基因或外显子中验证了两种类型的ESE：富含嘌呤的ESE（更为常见）和非富含嘌呤的ESE。相比之下，在大约20个基因或外显子中鉴定出的ESS序列高度多样，彼此之间几乎没有相似性。通过与细胞剪接因子相互作用，ESE或ESS决定了一个受调节的剪接位点（通常是上游3'剪接位点）是否会用于RNA剪接。然而，这些元件在选择受调节的剪接位点时如何精确发挥作用，目前仅部分得到了解。剪接位点选择的正调控和负调控之间的平衡可能取决于顺式元件的特性以及生理或病理条件下细胞剪接因子的变化。
