title: Regulation of 7B2 mRNA translation: dissecting the role of its 5'-untranslated region.
abstract: 7B2 is a chaperone for the prohormone/proneuropeptide convertase PC2. Its mRNA is readily detectable in most neuronal and endocrine cells; the protein, in contrast, is often found at relatively low levels, suggesting that translation of the corresponding mRNA may be repressed. Because the 5' untranslated region (5'-UTR) of this mRNA is relatively long and burdened with multiple AUGs, it has been speculated that it contributes to this repression. In this report, the influence of this region was assessed using in vitro and ex vivo approaches. The results showed that, in a cell-free system, full-length 7B2 mRNA was a poor template for translation. Its translatability dramatically improved when its 5'-UTR was truncated or when it was replaced with the 5'-UTR of carboxypeptidase E mRNA. These observations were confirmed in transfected mouse insulinoma MIN6 cells and human embryonic kidney HEK293 cells. Acute exposure of MIN6 cells to high glucose increased endogenous 7B2 biosynthesis without affecting the levels of its mRNA, suggesting that translation repression of this mRNA can be relieved by physiological stimuli.
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. hbtadros@hotmail.com
authors.forename: Haidy
authors.initials: H
authors.lastname: Tadros
authors.forename: Gunther
authors.initials: G
authors.lastname: Schmidt
authors.forename: Francine
authors.initials: F
authors.lastname: Sirois
authors.forename: Majambu
authors.initials: M
authors.lastname: Mbikay
mesh_terms: D020121:5' Untranslated Regions / Q000502:physiology*; D000818:Animals; D043423:Carboxypeptidase H / Q000378:metabolism; D045744:Cell Line, Tumor; D002474:Cell-Free System / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007340:Insulinoma / Q000378:metabolism; D051379:Mice; D051859:Neuroendocrine Secretory Protein 7B2 / Q000096:biosynthesis* / Q000378:metabolism; D045706:Proprotein Convertase 2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D014162:Transfection
chemical_list: D020121:5' Untranslated Regions; D051859:Neuroendocrine Secretory Protein 7B2; D012333:RNA, Messenger; C497678:SCG5 protein, human; C497679:Sgne1 protein, mouse; D043423:Carboxypeptidase H; D045706:Proprotein Convertase 2