Leptin receptor 5'untranslated regions in the rat: relative abundance, genomic organization and relation to putative response elements.
Hypothalamic sensitivity to leptin has been suggested to be important for regulation of body fat mass. Mice heterozygous for a mutation in the leptin receptor (leptin-R) have an increased body fat mass suggesting that the abundance of leptin-R may be an important determinator of leptin sensitivity. Leptin-R cDNAs from several species contain alternative 5'untranslated regions (5'UTRs), suggesting that several distinct regulatory regions may exist. To investigate possible mechanisms by which leptin-R expression may be regulated, we searched for possible alternative 5'UTRs of the leptin-R in the rat and determined their location in relation to putative response elements. Four leptin-R 5'UTRs (exons 1A-1D), which diverged 23 bp upstream of the start codon, were identified by 5'Rapid Amplification of cDNA Ends (5'RACE) and sequencing. Exons 1B and 1C were present in 31 and 61%, respectively, of all leptin-R transcripts in the hypothalamus as determined by a ribonuclease protection assay. Analysis of the 5' flanking genomic sequences revealed an imperfect estrogen response element (ERE), two Spl-sites, three CCAAT-boxes and one octamer. Exons 1A and 1D corresponded to a putative second gene, encoding the OB-Receptor Gene Related Protein (OB-RGRP), which is transcribed from a promoter shared with the leptin-R. DNA sequencing revealed that the rat OB-RGRP had 98 and 97% homology with the mouse and human sequence, respectively. We report here that transcription of the rat leptin-R gene may generate transcripts with four alternative 5'UTRs. The presence of a putative ERE, close to the most frequently used transcriptional start sites of the leptin-R gene in the hypothalamus, provides a possible mechanism by which estrogen may exert its effects on food intake.
Lindell
K
K
Research Centre for Endocrinology and Metabolism (RCEM), Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, Göteborg University, SE-413 45, Göteborg, Sweden.
Bennett
P A
PA
Itoh
Y
Y
Robinson
I C
IC
Carlsson
L M
LM
Carlsson
B
B
D020121:5' Untranslated Regions / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D016678:Genome; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D051381:Rats / Q000235:genetics*; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D020218:Response Elements / Q000235:genetics; D016415:Sequence Alignment; D014018:Tissue Distribution
D020121:5' Untranslated Regions; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C515448:LEPR protein, human; C484582:Leprot protein, rat; C484581:Obrgrp protein, mouse; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C515447:leptin receptor, mouse