Regulation of protein diversity by alternative pre-mRNA splicing with specific focus on chondrogenesis.
Regulation of protein diversity by alternative pre-mRNA splicing with specific focus on chondrogenesis.
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DOI：
10.1002/bdrc.20004
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发表时间：
2004-03-01
期刊：
影响因子：
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通讯作者：
Sandell, Linda J
中科院分区：
文献类型：
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作者：
McAlinden, Audrey;Havlioglu, Necat;Sandell, Linda J
对人类基因组的分析表明，大多数蛋白质多样性是由pre-mRNA的选择性剪接产生的。这种强大而通用的机制控制着单个基因在特定发育阶段可能需要的功能不同的蛋白质异构体的合成。因此，调节这种剪接机制的普遍存在和/或组织特异性RNA剪接因子为定义细胞分化过程中的表型特征提供了基础。在这篇综述中，我们将介绍pre-mRNA选择性剪接的基本机制，描述这一过程如何受到特定RNA剪接因子的调节，并将其与各种细胞分化系统联系起来。软骨形成是骨骼形成所必需的一个明确的分化途径，我们将详细讨论，重点是一些已知在软骨发育过程中表达的选择性剪接蛋白。我们提出了一个启发式的观点，最终，是这些RNA剪接因子的调节决定了细胞的分化状态。在pre-mRNA选择性剪接水平上研究调控将为了解有多少发育机制受到控制提供宝贵的见解，从而使我们能够操纵一个系统来选择特定的分化途径。
Analysis of the human genome has dramatically demonstrated that the majority of protein diversity is generated by alternative splicing of pre-mRNA. This powerful and versatile mechanism controls the synthesis of functionally different protein isoforms that may be required during specific stages of development from a single gene. Consequently, ubiquitous and/or tissue-specific RNA splicing factors that regulate this splicing mechanism provide the basis for defining phenotypic characteristics of cells during differentiation. In this review, we will introduce the basic mechanisms of pre-mRNA alternative splicing, describe how this process is regulated by specific RNA splicing factors, and relate this to various systems of cell differentiation. Chondrogenesis, a well-defined differentiation pathway necessary for skeletogenesis, will be discussed in detail, with focus on some of the alternatively-spliced proteins known to be expressed during cartilage development. We propose a heuristic view that, ultimately, it is the regulation of these RNA splicing factors that determines the differentiation status of a cell. Studying regulation at the level of pre-mRNA alternative splicing will provide invaluable insights into how many developmental mechanisms are controlled, thus enabling us to manipulate a system to select for a specific differentiation pathway.