Abstract
Transcriptional and post-transcriptional regulation of CFTR (cystic fibrosis transmembrane conductance regulator) gene expression was studied in HT29 cells. It is known that the abundance of CFTR mRNA increases during differentiation of pluripotent HT29-18 cells and is maintained at high levels in the stably differentiated HT29-18-C1 subclone. Nuclear run-on assays suggest that increased transcription of the CFTR gene explains the increased abundance of total CFTR mRNA in differentiated HT29 cells. The increased transcription cannot be ascribed to cell cycle-dependent expression of the CFTR gene or to changes in CFTR gene copy number between subcloned cells. Similar to native tissue cells, differentiated HT29 cells contain low copy numbers of CFTR transcripts (1-5/cell), and a portion of the CFTR transcripts are alternatively spliced to remove exon 9 (and make 9-mRNA). During differentiation of HT29-18 cells, the absolute amount of full-length CFTR mRNA increases 8-fold, whereas the amount of 9- mRNA increases 18-fold. The fraction of 9- mRNA in the CFTR mRNA pool is increased in differentiated HT29 cells. The results show that gene transcription regulates the abundance of CFTR transcripts and that regulatory control of alternative RNA splicing may also be a cellular mechanism to modulate CFTR function.
Highlights
CFTR gene explains the increased abundanceof total CFTR mRNA indifferentiatedHT29 cells
The results show that genetranscriptionregulatesthe abundance of CFTR transcripts and that regulatory control of alternative RNA splicing may be acellular mechanism to modulate CFTR function
Cystic fibrosis (CF)’ is a lethal autosomal recessive disease which affects epithelial function in a number of tissues, including those of the intestinal tract [1].The cystic fibrosis increased CFTR mRNA abundance [12]. It isknown that in HT29 cells, CFTR proteinis present in the plasma membrane [18],and increased CFTR mRNA abundance in differentiated cells is accompanied by an increase in CFTR protein [17]
Summary
Vol 267, No 27, Issue of September 25, pp. 1P9r2i9n9te-1d9i3n05U,1.S99.A2. Regulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene Transcription and AlternativReNA Splicing ina Model of Developing Intestinal Epithelium*. Since the intestinal epithelium contains multiple epithelial absolute amountof full-length CFTR mRNA increases cell types Cystic fibrosis (CF)’ is a lethal autosomal recessive disease which affects epithelial function in a number of tissues, including those of the intestinal tract [1].The cystic fibrosis increased CFTR mRNA abundance [12]. It isknown that in HT29 cells, CFTR proteinis present in the plasma membrane [18],and increased CFTR mRNA abundance in differentiated cells is accompanied by an increase in CFTR protein [17].
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