Alternative mRNA splicing: the Shaker gene.
Alternative mRNA splicing: the Shaker gene.
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替代 mRNA 剪接：Shaker 基因。
DOI：
10.1016/0168-9525(88)90105-9
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
R. Milner
中科院分区：
文献类型：
--
作者：
J. Sutcliffe;R. Milner
在过去的十年中，分子生物学的一个令人惊讶的发现是，一个基因可以通过选择性的mRNA剪接过程产生一个以上的成熟mRNA。这种现象发生在相当大比例的基因中：例如，在主要在神经系统中表达的已知基因中，约30%利用选择性剪接。大多数选择性剪接事件影响编码蛋白质的mRNA区域，因此该过程的一个生物学基本原理是显而易见的：选择性mRNA编码的蛋白质彼此具有许多共同特征，但在选择性剪接区域所具有的那些性质方面有所不同。因此，一个基因的选择性蛋白质产物代表一个蛋白质家族。钾通道选择性剪接的功能意义在电压门控钾通道的分子研究中非常明显。动作电位由轴突膜的去极化启动，其激活内向Na+传导。动作电位是自限性的，因为随着膜变得去极化，K+向外流动的电导也增加，从而在0.2-0.5 ms后恢复膜电位和Na+电导的静息值。几种K+通道介导膜复极化，并且已经发现这些通道在其电生理学性质上不同，特别是在它们引起复极化的速率上。由于神经末梢去极化的持续时间决定了释放的递质的量，因此在特定末梢表达的K+通道的类型可以指定其突触相互作用的强度。为了了解K+通道的电生理特性的变化，必须了解不同通道类型的生物化学性质。然而，当时既没有抗体
One of the surprising findings from the past decade of molecular biology researchis that a single gene can give rise to more than one mature mRNA via the process of alternative mRNA splicing. This phenomenon occurs in a substantial proportion of genes: for example, of known genes expressed predominantly in the nervous system, some 30% utilize alternative splicing. Most alternative splicing events affect the region of the mRNA that encodes protein, thus one biolo~ cal rationale for this process is apparent: the alternative mRNAs encode proteins that share many characteristics with each other but differ in those properties harbored by the alternatively ceded regions. Thus, the alternative protein products of a gene represent a protein family.Potassium channels The functional significance of alternative splicing is made extremely evident in molecular studies of voltage-gated potassium channels. Action potentials are initiated by depolarizations of the axon membrane that activate an inward Na+ conductance. Action potentials are self-limiting in that, as membranes become depolarized, the conductance to outward flow of K+ also increases, thereby restoring, after 0.2-0.5 ms, the membrane potential and the resting,; alue of the Na+ conductance. Several K+ channels mediate membrane repolarization and these have been found to vary in their electrophysiological properties, specifically in the rates at which they cause repolarization. Because the duration of depolarization at nerve terminals determines the amount of transmitter released, the type of K+ channel expressed at a particular terminal may specify the strength of its synaptic interaction. To understand the variation in the electrophysiological properties of K+ channels, it was essential to understand the biochemical nature of the different channel types. However, at the time there was neither antibody