Polymorphic GGC repeat differentially regulates human reelin gene expression levels.
The human gene encoding Reelin (RELN), a pivotal protein in neurodevelopment, includes a polymorphic GGC repeat in its 5' untranslated region (UTR). CHO cells transfected with constructs encompassing the RELN 5'UTR with 4-to-13 GGC repeats upstream of the luciferase reporter gene show declining luciferase activity with increasing GGC repeat number (P < 0.005), as predicted by computer-based simulations. Conversely, RELN 5'UTR sequences boost reporter gene expression above control levels in neuronal SN56 and N2A cell lines, but 12- and 13-repeat alleles still yield 50-60% less luciferase activity compared to the more common 8- and 10-repeat alleles (P < 0.0001). RELN "long" GGC alleles significantly blunt gene expression and may, through this effect, confer vulnerability to human disorders, such as schizophrenia and autism.
Persico
A M
AM
Laboratory of Molecular Psychiatry and Neurogenetics, University "Campus Bio-Medico", Rome, Italy.
Levitt
P
P
Pimenta
A F
AF
D020121:5' Untranslated Regions / Q000235:genetics*; D000818:Animals; D016466:CHO Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*; D014162:Transfection; D018911:Trinucleotide Repeats
D020121:5' Untranslated Regions; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases