Cell Shape-dependent Regulation of Protein 4.1 Alternative Pre-mRNA Splicing in Mammary Epithelial Cells

P. Olivier Schischmanoff; Paul Yaswen; Marilyn K Parra; Gloria Lee; Joel A Chasis; Narla Mohandas; John G Conboy

doi:10.1074/jbc.272.15.10254

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Cell Shape-dependent Regulation of Protein 4.1 Alternative Pre-mRNA Splicing in Mammary Epithelial Cells

Journal article

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Cell Shape-dependent Regulation of Protein 4.1 Alternative Pre-mRNA Splicing in Mammary Epithelial Cells

P. Olivier Schischmanoff, Paul Yaswen, Marilyn K Parra, Gloria Lee, Joel A Chasis, Narla Mohandas and John G Conboy

The Journal of biological chemistry, Vol.272(15), pp.10254-10259

04/1997

DOI: 10.1074/jbc.272.15.10254

PMID: 9092575

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Abstract

Expression of the complex gene encoding multiple isoforms of structural protein 4.1 is regulated by alternative pre-mRNA splicing. During erythropoiesis, developmental stage-specific inclusion of exon 16 generates protein 4.1 isoforms having a fully functional spectrin-actin binding domain. Here we show that human mammary epithelial cells (HMEC), coincident with the dramatic morphological changes induced by altered culture conditions, exhibit a novel pre-mRNA splicing switch involving a new exon (exon 17B, 450 nucleotides) in the COOH-terminal coding region. 4.1 RNA expressed in proliferating HMEC adherent to culture dishes mostly excluded exon 17B, whereas 4.1 transcripts processed in nondividing suspension cultures of HMEC strongly included this exon. This pre-mRNA splicing switch was reversible: cells transferred from poly(2-hydroxyethyl methacrylate) back to plastic resumed cell division and down-regulated exon 17B expression. More detailed studies revealed complex tissue-specific alternative splicing of exon 17B and another new exon 17A (51 nucleotides). These results predict the existence of multiple 4.1 protein isoforms with diverse COOH termini. Moreover, they strongly suggest that regulation of gene expression during differentiation of epithelial cells is mediated not only by transcriptional mechanisms, but also by post-transcriptional processes such as alternative pre-mRNA splicing.

Details

Title: Subtitle: Cell Shape-dependent Regulation of Protein 4.1 Alternative Pre-mRNA Splicing in Mammary Epithelial Cells
Creators: P. Olivier Schischmanoff
Paul Yaswen
Marilyn K Parra
Gloria Lee
Joel A Chasis
Narla Mohandas
John G Conboy
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.272(15), pp.10254-10259
DOI: 10.1074/jbc.272.15.10254
PMID: 9092575
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Language: English
Date published: 04/1997
Academic Unit: Iowa Neuroscience Institute; Immunology; Internal Medicine
Record Identifier: 9984070795702771

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