Tissue- and development-specific alternative RNA splicing regulates expression of multiple isoforms of erythroid membrane protein 4.1.
Tissue- and development-specific alternative RNA splicing regulates expression of multiple isoforms of erythroid membrane protein 4.1.
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DOI：
10.1016/s0021-9258(18)92973-x
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发表时间：
1991-05
期刊：
影响因子：
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通讯作者：
J. Conboy;J. Chan;J. Chasis;Y. Kan;N. Mohandas
中科院分区：
文献类型：
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作者：
J. Conboy;J. Chan;J. Chasis;Y. Kan;N. Mohandas
蛋白4.1，一种多功能结构蛋白，最初被描述为红细胞膜骨架的80 kDa组分，在分子量、亚细胞定位和一级氨基酸序列方面表现出组织和发育特异性异质性。早期的报道表明，这种令人印象深刻的异质性中的一些是由选择性RNA剪接产生的（Conboy，J.G.，陈，J.，Mohandas，N.，和Kan，Y. W.等人（1988）Proc. Acad. Sci.联合S. A. 85，9062-9065; Tang，T. K.，Leto，T.，Marchesi，V. T.，和Benz，E. J.（1990）J. Cell Biol.110，617-624）。我们现在已经完成了系统的分析4.1在红细胞中表达的mRNA亚型，并产生了一个“选择性剪接图”，其中概括了大量的多肽亚型可能产生的9个选择性外显子的组合剪接。复杂的5'剪接事件产生mRNA亚型，其可以在不同位点启动翻译，从而产生延长或截短的NH 2末端;在红细胞和T淋巴细胞中均检测到延长的约135-kDa和原型的约80-kDa物质，但比例非常不同。在4.1负责与其他膜骨架元件相互作用的功能域中，预测了10 kDa血影蛋白-肌动蛋白结合区的四种变体和推定的30 kDa血型糖蛋白结合区的四种变体。在血影蛋白-肌动蛋白结合区发育控制的RNA剪接可能有助于调节红细胞生成过程中发生的膜结构和机械性能的重塑。
Protein 4.1, a multifunctional structural protein originally described as an 80-kDa component of the erythroid membrane skeleton, exhibits tissue- and development-specific heterogeneity in molecular weight, subcellular localization, and primary amino acid sequence. Earlier reports suggested that some of this impressive heterogeneity is generated by alternative RNA splicing (Conboy, J. G., Chan, J., Mohandas, N., and Kan, Y. W. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 9062-9065; Tang, T. K., Leto, T., Marchesi, V. T., and Benz, E. J. (1990) J. Cell Biol. 110, 617-624). We have now completed a systematic analysis of 4.1 mRNA isoforms expressed in erythroid cells, and have generated an “alternative splicing map” which summarizes diagrammatically a multitude of polypeptide isoforms potentially generated by combinatorial splicing of nine alternative exons. Complex 5' splicing events yield mRNA isoforms that may initiate translation at different sites and thus generate elongated or truncated NH2 termini; elongated approximately 135-kDa and prototypical approximately 80-kDa species were detected in both erythrocytes and T-lymphocytes, but in very different ratios. Among the functional domains of 4.1 responsible for interaction with other membrane skeletal elements, four variants of the 10-kDa spectrin-actin-binding region and four variants of the putative 30-kDa glycophorin-binding region are predicted. Developmentally controlled alternative RNA splicing in the spectrin-actin-binding region may help regulate remodeling of membrane architecture and mechanical properties that occur during erythropoiesis.