Pagani F, Zagato L, Vergani C, Casari G, Sidoli A, Baralle F E
Fondazione Rivetti, Laboratory of Biochemistry and Molecular Biology, Milan, Italy.
J Cell Biol. 1991 Jun;113(5):1223-9. doi: 10.1083/jcb.113.5.1223.
Fibronectin isoforms are generated by the alternative splicing of a primary transcript derived from a single gene. In rat at least three regions of the molecule are involved: EIIIA, EIIIB, and V. This study investigated the splicing patterns of these regions during development and aging, by means of ribonuclease protection analysis. Between fetal and adult rat, the extent of inclusion of the EIIIA and/or EIIIB region in fibronectin mRNA varied according to the type of tissue analyzed; but the inclusion of the V region, and in particular the V25 alternative variant, was significantly higher in all fetal than in adult tissues. These data suggest a crucial role of the V25 variant, possibly related to its interaction with the alpha 4 beta 1 integrin receptor during development. On the other hand, during aging, the only significant change observed in the splicing pattern was a decrease in the EIIIA variant in brain. The high inclusion levels of the EIIIA and EIIIB regions in young adult brain suggest that these segments may play an important role in differentiated brain tissue. The decreasing levels of inclusion of the EIIIA segment in brain fibronectin mRNA during aging may be an age-related marker with functional consequences.
纤连蛋白异构体是由单个基因的初级转录本的可变剪接产生的。在大鼠中,分子的至少三个区域参与其中:EIIIA、EIIIB和V。本研究通过核糖核酸酶保护分析,研究了这些区域在发育和衰老过程中的剪接模式。在胎儿大鼠和成年大鼠之间,纤连蛋白mRNA中EIIIA和/或EIIIB区域的包含程度根据所分析的组织类型而有所不同;但是V区域,特别是V25可变变体,在所有胎儿组织中的包含率显著高于成年组织。这些数据表明V25变体具有关键作用,可能与其在发育过程中与α4β1整合素受体的相互作用有关。另一方面,在衰老过程中,剪接模式中唯一观察到的显著变化是大脑中EIIIA变体的减少。年轻成年大脑中EIIIA和EIIIB区域的高包含水平表明这些片段可能在分化的脑组织中起重要作用。衰老过程中脑纤连蛋白mRNA中EIIIA片段的包含水平下降可能是一个与年龄相关的具有功能后果的标志物。