Leptin receptor 5'untranslated regions in the rat: relative abundance, genomic organization and relation to putative response elements

Mol Cell Endocrinol. 2001 Feb 14;172(1-2):37-45. doi: 10.1016/s0303-7207(00)00382-8.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / analysis*
  • 5' Untranslated Regions / metabolism
  • Animals
  • Base Sequence
  • Carrier Proteins / genetics*
  • Exons
  • Female
  • Genome
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Rats / genetics*
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface*
  • Receptors, Leptin
  • Response Elements / genetics
  • Sequence Alignment
  • Tissue Distribution

Substances

  • 5' Untranslated Regions
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Leprot protein, rat
  • Obrgrp protein, mouse
  • Receptors, Cell Surface
  • Receptors, Leptin
  • leptin receptor, human
  • leptin receptor, mouse

Associated data

  • GENBANK/AF121331
  • GENBANK/AF121332
  • GENBANK/AF121333
  • GENBANK/AF139208