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
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.