Glucagon gene 3'-flanking sequences direct formation of proglucagon messenger RNA 3'-ends in islet and nonislet cells lines.
Glucagon and the glucagon-like peptides are encoded within a larger precursor, proglucagon. Transcription of the glucagon gene in pancreas, intestine, and brain gives rise to identical proglucagon mRNA transcripts, after which tissue-specific post-translational processing produces different profiles of proglucagon-derived peptides in each tissue. The importance of glucagon gene 3'-untranslated and 3'-flanking sequences in the control of glucagon mRNA production was studied by transfecting a series of 3'-deleted glucagon genes into fibroblast and islet cell lines. Glucagon genes containing 2 kilobases of 3'-flanking sequences gave rise to accurately processed mRNA transcripts in both baby hamster kidney fibroblasts and InR1-G9 islet cell lines. Deletion of all but 50 basepairs of 3'-flanking sequence had no effect on glucagon mRNA 3'-end formation. In contrast, additional deletion of 3'-flanking and 3'-untranslated sequences resulted in the production of read-through mRNA transcripts with aberrant 3'-ends. The results of these studies define a 50-basepair region in the 3'-flanking sequence of the glucagon gene important for the accurate processing of proglucagon mRNA transcripts.
Lee
Y C
YC
Department of Medicine, Toronto General Hospital, University of Toronto, Ontario, Canada.
Drucker
D J
DJ
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005934:Glucagon / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D007668:Kidney / Q000166:cytology* / Q000378:metabolism; D008969:Molecular Sequence Data; D052336:Proglucagon; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D011498:Protein Precursors; D012333:RNA, Messenger; D052336:Proglucagon; D004247:DNA; D005934:Glucagon