CELL SHAPE-DEPENDENT REGULATION OF PROTEIN-4.1 ALTERNATIVE PRE-MESSENGER-RNA SPLICING IN MAMMARY EPTHELIAL CELLS

Citation
Po. Schischmanoff et al., CELL SHAPE-DEPENDENT REGULATION OF PROTEIN-4.1 ALTERNATIVE PRE-MESSENGER-RNA SPLICING IN MAMMARY EPTHELIAL CELLS, The Journal of biological chemistry, 272(15), 1997, pp. 10254-10259
Citations number
42
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
272
Issue
15
Year of publication
1997
Pages
10254 - 10259
Database
ISI
SICI code
0021-9258(1997)272:15<10254:CSROPA>2.0.ZU;2-J
Abstract
Expression of the complex gene encoding multiple isoforms of structura l protein 4.1 is regulated by alternative pre-mRNA splicing During ery thropoiesis, developmental stage-specific inclusion of exon 16 generat es protein 4.1 isoforms having a fully functional spectrinactin bindin g domain, Here we show that human mammary epithelial cells (HMEC), coi ncident with the dramatic morphological changes induced by altered cul ture conditions, exhibit a novel pre-mRNA splicing switch involving a new exon (exon 17B, 450 nucleotides) in the COOH-terminal coding regio n, 4.1 RNA expressed in proliferating HMEC adherent to culture dishes mostly excluded exon 17B, whereas 4.1 transcripts processed in nondivi ding suspension cultures of HMEC strongly included this exon, This pre -mRNA splicing switch was reversible: cells transferred from poly(2-hy droxyethyl methacrylate) back to plastic resumed cell division and dow n-regulated exon 17B expression, More detailed studies revealed comple x tissue-specific alternative splicing of exon 17B and another new exo n 17A (51 nucleotides), These results predict the existence of multipl e 4.1 protein isoforms with diverse COOH termini, Moreover, they stron gly 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 m RNA splicing.