Alternative precursor messenger RNA (pre-mRNA) splicing plays a pivotal role in the flow of genetic information from DNA to proteins by expanding the coding capacity of genomes. Regulation of alternative splicing is as important as regulation of transcription to determine cell- and tissue-specific features, normal cell functioning, and responses of eukaryotic cells to external cues. Its importance is confirmed by the evolutionary conservation and diversification of alternative splicing and the fact that its deregulation causes hereditary disease and cancer. This review discusses the multiple layers of cotranscriptional regulation of alternative splicing in which chromatin structure, DNA methylation, histone marks, and nucleosome positioning play a fundamental role in providing a dynamic scaffold for interactions between the splicing and transcription machineries. We focus on evidence for how the kinetics of RNA polymerase II (RNAPII) elongation and the recruitment of splicing factors and adaptor proteins to chromatin components act in coordination to regulate alternative splicing.

Cellular and plasma fibronectins are heterodimers consisting of similar but not identical polypeptides. The differences between fibronectin subunits are due in part to the variability of internal primary sequences. This results from alternative splicing in at least two regions (ED and IIICS) of the pre‐mRNA. The complete primary structure of human fibronectin, including most of the internal variations, has been determined by sequencing a series of overlapping cDNA clones. In total, they covered 7692 nucleotides and represented the mRNA sequence coding from the amino terminus of the mature protein to the poly(A) tail. The deduced amino acid sequence of fibronectin has been analysed in terms of the arrangement of internal homologies and the different binding domains.

The fibronectin (FN) gene has become paradigmatic to illustrate genome evolution by exon shuffling, generation of protein diversity by alternative mRNA splicing, and topological coordination between transcription and splicing. Alternative splicing in three sites of the primary transcript gives rise to multiple FN polypeptides. This process is cell type-, development- and age-regulated. The different FN variants seem to play specific roles in FN dimer secretion, blood clotting, adhesion to lymphoid cells, skin wound healing, atherosclerosis, and liver fibrosis. This review focuses on function assignment to the alternatively spliced segments, as well as on the external signals and cis-acting sequences that control the mechanisms of alternative splicing. We also discuss FN transcriptional regulation in response to viral transformation, growth factors, and cyclic AMP in the light of promoter architecture and its interaction with specific transcription factors. The relevance of FN RNA "tracks" as assembly lines of coordinated transcription and RNA processing is also addressed.

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