Tissue-specific splicing pattern of fibronectin messenger RNA precursor during development and aging in rat.

Abstract

Abstract.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 c~4~1 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. CELL-to-cell and cell-to-substrate interactions play a fundamental role in cell behavior, division, and differentiation. Among the extracellular components involved in these events, fibronectin (FN) ~ is probably one of the most important and widely distributed. Fibronectin is a dimeric high molecular weight glycoprotein found in blood, lymph, and tissue fluids, as well as in association with basement membranes, connective tissue matrices and the extracellular matrix of many cells (23, 37).The primary structure of FN has been described at both protein (human and bovine FN) and cDNA (chicken, rat, and human FN) levels (4, 13-15, 21, 26, 32, 33, 40, 41, 43, 45). The FN molecule is composed of three different kinds of repeated sequence, known as types I, II and III with a characteristic modular structure (21,33,40,41,43). These repeats are assembled into a series of structural domains, each having a distinct binding activity toward collagen, sulfated glycosaminoglycans, fibrin, and the cell surface receptors collectively termed integrins (19,36,49).FN molecules are a mixture of several protein types that differ both in their primary structure, and in their posttranslational modifications. All of the sequence variations are produced by the alternative processing of a common mRNA precursor (pre-mRNA) transcribed from a single gene and 1. Abbreviation used in this paper: FN, fibronectin. differentially spliced in the various cell types (1,18,30,40,41,45,50).Three sites of alternative splicing have so far been described: ED-A, ED-B, and IIICS in human FN and the corresponding sites (EIIIA, EIIIB, and V) in rat FN. EIIIA and EIIIB share a common gene structure and, in both cases, alternative splicing leads to the insertion of an additional exon coding for a type III homology domain. The V region in ...

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