International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
FEBS J. 2010 Feb;277(4):841-55. doi: 10.1111/j.1742-4658.2009.07520.x. Epub 2010 Jan 15.
What makes a nucleotide sequence an exon (or an intron) is a question that still lacks a satisfactory answer. Indeed, most eukaryotic genes are full of sequences that look like perfect exons, but which are nonetheless ignored by the splicing machinery (hence the name 'pseudoexons'). The existence of these pseudoexons has been known since the earliest days of splicing research, but until recently the tendency has been to view them as an interesting, but rather rare, curiosity. In recent years, however, the importance of pseudoexons in regulating splicing processes has been steadily revalued. Even more importantly, clinically oriented screening studies that search for splicing mutations are beginning to uncover a situation where aberrant pseudoexon inclusion as a cause of human disease is more frequent than previously thought. Here we aim to provide a review of the mechanisms that lead to pseudoexon activation in human genes and how the various cis- and trans-acting cellular factors regulate their inclusion. Moreover, we list the potential therapeutic approaches that are being tested with the aim of inhibiting their inclusion in the final mRNA molecules.
是什么使核苷酸序列成为外显子（或内含子），这个问题仍然没有一个令人满意的答案。事实上，大多数真核基因都充满了看起来像完美外显子的序列，但这些序列却被剪接机制所忽略（因此被称为“假外显子”）。自剪接研究的早期以来，人们就已经知道这些假外显子的存在，但直到最近，人们一直倾向于将它们视为一种有趣但相当罕见的好奇心。然而，近年来，假外显子在调节剪接过程中的重要性逐渐得到重新评估。更重要的是，以剪接突变为目标的临床导向筛选研究开始揭示，异常假外显子的包含作为人类疾病的一个原因比以前认为的更为频繁。在这里，我们旨在综述导致人类基因中假外显子激活的机制，以及各种顺式和反式作用的细胞因子如何调节它们的包含。此外，我们列出了正在测试的潜在治疗方法，旨在抑制它们在最终的 mRNA 分子中的包含。
