Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Biochemistry. 2012 Jul 17;51(28):5541-56. doi: 10.1021/bi3007065. Epub 2012 Jun 29.
Alternative splicing (AS) of RNA is a key mechanism for diversification of the eukaryotic proteome. In this process, different mRNA transcripts can be produced through altered excision and/or inclusion of exons during processing of the pre-mRNA molecule. Since its discovery, AS has been shown to play roles in protein structure, function, and localization. Dysregulation of this process can result in disease phenotypes. Moreover, AS pathways are promising therapeutic targets for a number of diseases. Integral membrane proteins (MPs) represent a class of proteins that may be particularly amenable to regulation by alternative splicing because of the distinctive topological restraints associated with their folding, structure, trafficking, and function. Here, we review the impact of AS on MP form and function and the roles of AS in MP-related disorders such as Alzheimer's disease.
RNA 的可变剪接 (AS) 是真核生物蛋白质组多样化的关键机制。在此过程中，前体 mRNA 分子加工过程中通过改变外显子的剪接和/或包含，可以产生不同的 mRNA 转录本。自发现以来，AS 已被证明在蛋白质结构、功能和定位中发挥作用。该过程的失调可导致疾病表型。此外，AS 途径是许多疾病有前途的治疗靶点。整合膜蛋白 (MP) 是一类可能特别容易受到可变剪接调控的蛋白质，因为它们的折叠、结构、运输和功能与独特的拓扑限制有关。在这里，我们回顾了 AS 对 MP 形式和功能的影响，以及 AS 在与 MP 相关的疾病（如阿尔茨海默病）中的作用。
