Intron-mediated expression of the human neuropeptide Y Y1 receptor

• Published in: Molecular and cellular endocrinology Vol. 188; no. 1-2; pp. 85 - 97
• Main Authors: Marklund, Ulrica, Byström, Mona, Gedda, Karin, Larefalk, Asa, Juneblad, Kristina, Nyström, Susanne, Ekstrand, A Jonas
• Format: Journal Article
• Language: English
• Published: Ireland 25-02-2002
• Subjects: 5' Untranslated Regions; Animals; Binding, Competitive; Blotting, Northern; Cells, Cultured; Cyclic AMP - metabolism; DNA Primers - chemistry; Electrophoresis, Polyacrylamide Gel; Gene Deletion; Gene Expression - drug effects; Green Fluorescent Proteins; GTP-Binding Proteins - chemistry; Humans; Introns - genetics; Luminescent Proteins - metabolism; Microscopy, Confocal; Neuropeptides - chemistry; Neuropeptides - pharmacology; Peptide Fragments - immunology; Peptide Fragments - metabolism; Polymerase Chain Reaction; Rabbits; Receptors, Neuropeptide Y - genetics; Receptors, Neuropeptide Y - metabolism; RNA Splicing - physiology; RNA, Messenger - metabolism; Transduction, Genetic; Transfection
• ISSN: 0303-7207
• DOI: 10.1016/S0303-7207(01)00738-9

The Neuropeptide Y (NPY) family of neuropeptides exert their function through a family of heptahelical G-protein coupled receptors regulating essential physiological processes. A 97 base pair intron (intron IV) intervenes the coding sequence of the human NPY Y1 receptor (hY1) gene and was found frequently retained at variable levels in poly A+ mRNA isolated from multiple human tissues. When included in hY1 expression vectors, either in its natural position or 5' of the hY1 cDNA, intron IV mediated a significant increase of both hY1 mRNA and corresponding functional receptor protein in transfected mammalian cells, implying an in vivo regulatory function of the endogenous intron. Our results further indicate that the nuclear history of the hY1 pre-mRNA influence ectopic hY1 production through post-transcriptional mechanisms and argues against intron IV acting as a transcriptional enhancer as well as the possibility that a putative hY1 related 5TM accessory protein encoded by the non-spliced hY1 mRNA would facilitate hY1 production on a post-translational level.