Human Molecular Genetics, 2003, Vol. 12, No. 7 759-769
DOI: 10.1093/hmg/ddg079
© 2003 Oxford University Press
Alternative 5' exons of the CFTR gene show developmental regulation
Paediatric Molecular Genetics, Weatherall Institute of Molecular Medicine, Oxford University, John Radcliffe Hospital, Oxford, OX3 9DS, UK
Received November 29, 2002; Accepted January 29, 2003
The cystic fibrosis transmembrane conductance regulator (CFTR) gene shows a complex mechanism of tissue-specific and temporal regulation. Expression of the sheep and human CFTR genes shows a gradual decline during lung development, from the early mid-trimester through to term. Alternative upstream exons of CFTR have been identified in several species but their functional role remains obscure. We identified a novel 5' exon of the sheep CFTR gene (ov1a) that occurs in two splice forms (ov1aL and ov1aS), which are both mutually exclusive with exon 1. CFTR transcripts including ov1aL and ov1aS are present at low levels in many sheep tissues, however ov1aS shows temporal and spatial regulation during fetal lung development, being most abundant when CFTR expression levels start to decline. Alternative 5' exons -1a and 1a in the human CFTR gene also show changes in expression levels through lung development. Evaluation of ov1aL and ov1aS by Mfold reveals the potential to form extremely stable secondary structures which would cause ribosomal subunit detachment. Further, the loss of exon 1 from the CFTR transcript removes motifs that are crucial for normal trafficking of the CFTR protein. Recruitment of these alternative upstream exons may represent a novel mechanism of developmental regulation of CFTR expression.
* The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
To whom correspondence should be addressed. Email: aharris{at}molbiol.ox.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Rene, M. Taulan, F. Iral, J. Doudement, A. L'Honore, C. Gerbon, J. Demaille, M. Claustres, and M.-C. Romey Binding of serum response factor to cystic fibrosis transmembrane conductance regulator CArG-like elements, as a new potential CFTR transcriptional regulation pathway Nucleic Acids Res., September 16, 2005; 33(16): 5271 - 5290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L. Davies, J. I. Vandenberg, R. A. Sayeed, and A. E. O. Trezise Cardiac Expression of the Cystic Fibrosis Transmembrane Conductance Regulator Involves Novel Exon 1 Usage to Produce a Unique Amino-terminal Protein J. Biol. Chem., April 16, 2004; 279(16): 15877 - 15887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Chubanov, S. Waldegger, M. M. y Schnitzler, H. Vitzthum, M. C. Sassen, H. W. Seyberth, M. Konrad, and T. Gudermann Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia PNAS, March 2, 2004; 101(9): 2894 - 2899. [Abstract] [Full Text] [PDF]
|
|