Structure of the mouse leukaemia inhibitory factor receptor gene: regulated expression of mRNA encoding a soluble receptor isoform from an alternative 5' untranslated region.
The low-affinity leukaemia inhibitory factor receptor (LIF-R) is a component of cell-surface receptor complexes for the multifunctional cytokines leukaemia inhibitory factor, ciliary neurotrophic factor, oncostatin M and cardiotrophin-1. Both soluble and transmembrane forms of the protein have been described and several LIF-R mRNAs have been reported previously. In order to determine the coding potential of LIF-R mRNAs we have isolated and characterized the mouse LIF-R gene. mRNA encoding soluble LIF-R (sLIF-R) is formed by inclusion of an exon in which polyadenylation signals are provided by a B2 repeat. This exon is located centrally within the LIF-R gene but is excluded from the transmembrane LIF-R mRNA by alternative splicing. The transmembrane receptor is encoded by 19 exons distributed over 38 kb. Two distinct 5' non-coding exons have been identified, indicating the existence of alternative promoters. One of these is G/C rich and possesses a consensus initiator sequence as well as potential Sp1 binding sites. Expression of exon 1 from this promoter occurs in a wide variety of tissues, whereas expression of the alternative 5' untranslated region (exon 1a) is normally restricted to liver, the principal source of sLIF-R. During pregnancy expression of exon 1a becomes detectable also in the uterus. Expression of exon 1a increases dramatically during gestation and is accompanied by a similar quantitative rise in expression of sLIF-R mRNA. These findings establish that expression of LIF-R is under complex transcriptional control and indicate that regulated expression of the soluble cytokine receptor isoform may be due principally to an increase in the activity of a dedicated promoter.
Chambers
I
I
Centre for Genome Research, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JQ, Scotland, U.K.
Cozens
A
A
Broadbent
J
J
Robertson
M
M
Lee
M
M
Li
M
M
Smith
A
A
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006131:Growth Inhibitors; D015850:Interleukin-6; D007438:Introns / Q000235:genetics; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008099:Liver / Q000378:metabolism; D008222:Lymphokines; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics*; D053606:Receptors, OSM-LIF; D012260:Ribonucleases / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D012260:Ribonucleases