Hou V C, Conboy J G
Lawrence Berkeley National Laboratory, Life Sciences Division, Berkeley, California, USA.
Curr Opin Hematol. 2001 Mar;8(2):74-9. doi: 10.1097/00062752-200103000-00003.
Although the mature enucleated erythrocyte is no longer active in nuclear processes such as pre-mRNA splicing, the function of many of its major structural proteins is dependent on alternative splicing choices made during the earlier stages of erythropoiesis. These splicing decisions fundamentally regulate many aspects of protein structure and function by governing the inclusion or exclusion of exons that encode protein interaction domains, regulatory signals, or translation initiation or termination sites. Alternative splicing events may be partially or entirely erythroid-specific, ie, distinct from the splicing patterns imposed on the same transcripts in nonerythroid cells. Moreover, differentiation stage-specific splicing "switches" may alter the structure and function of erythroid proteins in physiologically important ways as the cell is morphologically and functionally remodeled during normal differentiation. Derangements in the splicing of individual mutated pre-mRNAs can produce synthesis of truncated or unstable proteins that are responsible for numerous erythrocyte disorders. This review will summarize the salient features of regulated alternative splicing in general, review existing information concerning the widespread extent of alternative splicing among erythroid genes, and describe recent studies that are beginning to uncover the mechanisms that regulate an erythroid splicing switch in the protein 4.1R gene.
尽管成熟的无核红细胞在诸如前体mRNA剪接等核过程中不再活跃，但其许多主要结构蛋白的功能取决于红细胞生成早期阶段所做出的可变剪接选择。这些剪接决定通过控制编码蛋白质相互作用结构域、调节信号或翻译起始或终止位点的外显子的包含或排除，从根本上调节蛋白质结构和功能的许多方面。可变剪接事件可能部分或完全是红细胞特异性的，即不同于非红细胞中相同转录本所采用的剪接模式。此外，随着细胞在正常分化过程中进行形态和功能重塑，分化阶段特异性剪接“开关”可能以生理上重要的方式改变红细胞蛋白的结构和功能。单个突变前体mRNA剪接的紊乱可产生截短或不稳定蛋白质的合成，这些蛋白质是导致许多红细胞疾病的原因。本综述将总结一般情况下受调控的可变剪接的显著特征，回顾关于红细胞基因中可变剪接广泛程度的现有信息，并描述最近开始揭示调节蛋白4.1R基因中红细胞剪接开关机制的研究。
