Fine structure of the murine leptin receptor gene: splice site suppression is required to form two alternatively spliced transcripts.
The fine structure of the murine leptin receptor gene (Lepr) is described. Duplicated ligand binding domains (conserved among cytokine receptors) are found in eight exons (coding exons 3 to 6 and 8 to 11). Thus, it is possible that a single leptin receptor molecule could have two functional ligand binding domains. The transmembrane region of Lepr is in coding exon 16 while the juxtamembrane JAK docking site is in coding exon 17. For all membrane-bound forms, the transcript must include 17 invariant exons and 1 alternatively spliced 3' terminal exon. The transcript encoding the soluble receptor (Re) includes 14 coding exons and an alternatively spliced 3' terminal exon. We have identified two splice variants (Rc and Re) for which there are no intervening sequences between the two final exons. This unusual juxtaposition of exons requires that splice donor sites at the 5' end of the respective terminal exons be ignored in the production of these splice variants. We suggest that splice site suppression is responsible for the formation of two of the alternatively spliced forms of the mouse Lepr gene. The juxtaposition of two coding exons separated by a consensus splice donor sequence is the structural substrate for this mode of alternative splicing. We present evidence that the Rc form is expressed in human tissues while the Re form, the soluble receptor, is not expressed.
Chua
S C
SC
Laboratory of Human Behavior and Metabolism, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Koutras
I K
IK
Han
L
L
Liu
S M
SM
Kay
J
J
Young
S J
SJ
Chung
W K
WK
Leibel
R L
RL
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D006801:Humans; D007438:Introns; D020738:Leptin; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine / Q000235:genetics*; D054411:Receptors, Leptin; D012091:Repetitive Sequences, Nucleic Acid
D002352:Carrier Proteins; D017931:DNA Primers; C515448:LEPR protein, human; D020738:Leptin; D011506:Proteins; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D004247:DNA