FINE-STRUCTURE OF THE MURINE LEPTIN RECEPTOR GENE - SPLICE-SITE SUPPRESSION IS REQUIRED TO FORM 2 ALTERNATIVELY SPLICED TRANSCRIPTS

The fine structure of the murine leptin receptor gene (Lepr) is descri bed. Duplicated ligand binding domains (conserved among cytokine recep tors) 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 i s in coding exon 16 while the juxtamembrane JAK docking site is in cod ing 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 (Re and Re) for which there are no intervening sequen ces between the two final exons. This unusual juxtaposition of exons r equires that splice donor sites at the 5' end of the respective termin al exons be ignored in the production of these splice variants. We sug gest that splice site suppression is responsible for the formation of two of the alternatively spliced forms of the mouse Lepr gene. The jux taposition of two coding exons separated by a consensus splice donor s equence is the structural substrate for this mode of alternative splic ing. We present evidence that the Re form is expressed in human tissue s while the Re form, the soluble receptor, is not expressed. (C) 1997 Academic Press.