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Regulation of alternative splicing in the IIICS region of human fibronectin pre-mRNA encoding cell binding sites CS1 and CS5.
J Cell Sci. 1992 Oct; 103 (Pt 2):423-33.JC

Abstract

The cell binding sites CS1 and CS5 in the IIICS region of human fibronectin (FN) mediate the adhesion of specific cell types by interacting with the integrin alpha 4 beta 1. IIICS pre-mRNA is alternatively spliced via the use of three alternative splice acceptor sites and one alternative splice donor site. These alternative splicing pathways can potentially give rise to variant FN molecules which are CS1+,CS5+; CS1+,CS5-; CS1-,CS5+ or CS1-,CS5-. Here we show that selection of the acceptor site which incorporates mRNA encoding CS1 and CS5 is more frequent in foetal tissues compared to adult liver, whereas an alternative acceptor site and the alternative donor site, which exclude CS1 and CS5, are used at a higher level in adult liver compared to foetal tissue. All possible splice junctions were accurately processed, and selected at different levels in mRNA expressed from a IIICS minigene transiently transfected into a HeLa cell line which does not express FN, suggesting that all the cellular factors required for alternative processing of IIICS are present in this system. Furthermore, pre-mRNA expressed from a mutant construct lacking IIICS-1 intron sequence, was correctly processed in HeLa cells via selection of all possible splice sites. On the basis of our results we propose that regulation of splice site selection in IIICS and thus expression of CS1 and CS5 is achieved by subtle tuning of splicing systems involving the interaction of local cis elements and cellular factors which are not necessarily restricted developmentally or tissue-specifically, and that expression of CS1 and CS5 is independently regulated.

Authors+Show Affiliations

Sir William Dunn School of Pathology, University of Oxford, UK.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1478944

Citation

Mardon, H J., and G Sebastio. "Regulation of Alternative Splicing in the IIICS Region of Human Fibronectin pre-mRNA Encoding Cell Binding Sites CS1 and CS5." Journal of Cell Science, vol. 103 (Pt 2), 1992, pp. 423-33.
Mardon HJ, Sebastio G. Regulation of alternative splicing in the IIICS region of human fibronectin pre-mRNA encoding cell binding sites CS1 and CS5. J Cell Sci. 1992;103 (Pt 2):423-33.
Mardon, H. J., & Sebastio, G. (1992). Regulation of alternative splicing in the IIICS region of human fibronectin pre-mRNA encoding cell binding sites CS1 and CS5. Journal of Cell Science, 103 (Pt 2), 423-33.
Mardon HJ, Sebastio G. Regulation of Alternative Splicing in the IIICS Region of Human Fibronectin pre-mRNA Encoding Cell Binding Sites CS1 and CS5. J Cell Sci. 1992;103 (Pt 2):423-33. PubMed PMID: 1478944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of alternative splicing in the IIICS region of human fibronectin pre-mRNA encoding cell binding sites CS1 and CS5. AU - Mardon,H J, AU - Sebastio,G, PY - 1992/10/1/pubmed PY - 1992/10/1/medline PY - 1992/10/1/entrez SP - 423 EP - 33 JF - Journal of cell science JO - J Cell Sci VL - 103 (Pt 2) N2 - The cell binding sites CS1 and CS5 in the IIICS region of human fibronectin (FN) mediate the adhesion of specific cell types by interacting with the integrin alpha 4 beta 1. IIICS pre-mRNA is alternatively spliced via the use of three alternative splice acceptor sites and one alternative splice donor site. These alternative splicing pathways can potentially give rise to variant FN molecules which are CS1+,CS5+; CS1+,CS5-; CS1-,CS5+ or CS1-,CS5-. Here we show that selection of the acceptor site which incorporates mRNA encoding CS1 and CS5 is more frequent in foetal tissues compared to adult liver, whereas an alternative acceptor site and the alternative donor site, which exclude CS1 and CS5, are used at a higher level in adult liver compared to foetal tissue. All possible splice junctions were accurately processed, and selected at different levels in mRNA expressed from a IIICS minigene transiently transfected into a HeLa cell line which does not express FN, suggesting that all the cellular factors required for alternative processing of IIICS are present in this system. Furthermore, pre-mRNA expressed from a mutant construct lacking IIICS-1 intron sequence, was correctly processed in HeLa cells via selection of all possible splice sites. On the basis of our results we propose that regulation of splice site selection in IIICS and thus expression of CS1 and CS5 is achieved by subtle tuning of splicing systems involving the interaction of local cis elements and cellular factors which are not necessarily restricted developmentally or tissue-specifically, and that expression of CS1 and CS5 is independently regulated. SN - 0021-9533 UR - https://www.unboundmedicine.com/medline/citation/1478944/Regulation_of_alternative_splicing_in_the_IIICS_region_of_human_fibronectin_pre_mRNA_encoding_cell_binding_sites_CS1_and_CS5_ DB - PRIME DP - Unbound Medicine ER -