A Mammalian Homolog of unc-53 Is Regulated by all-trans Retinoic Acid in Neuroblastoma Cells and Embryos

• Published in: Proceedings of the National Academy of Sciences - PNAS 2002-03, Vol.99 (6), p.3422-3427
• Main Authors: Merrill, R. A., Plum, L. A., Kaiser, M. E., Clagett-Dame, M.
• Format: Article
• Language: English
• Subjects: Aging - metabolism; Amino Acid Sequence; Animals; Biological Sciences; Biology; Caenorhabditis elegans - chemistry; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell lines; Chemistry; chromosome 11; Chromosomes, Human, Pair 11 - genetics; Cloning, Molecular; Complementary DNA; Embryo, Mammalian - metabolism; Embryo, Nonmammalian; Embryos; Exons - genetics; Gene Expression Profiling; Gene Expression Regulation, Developmental; Hindbrain; Humans; In Situ Hybridization; Messenger RNA; Molecular Sequence Data; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nervous System - metabolism; Neuroblastoma; Neuroblastoma - genetics; Neuroblastoma - metabolism; Neurons; Nucleotides; Physical Chromosome Mapping; RAINB1 gene; RAINB1 protein; Rats; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tretinoin - administration & dosage; Tretinoin - pharmacology; Tumor Cells, Cultured; unc-53 gene; Up-Regulation - drug effects; Vitamin A
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.052017399

The vitamin A metabolite, all-trans retinoic acid (atRA), plays an important role in neuronal development, including neurite outgrowth. However, the genes that lie downstream of atRA and its receptors in neuronal cells are largely unknown. By using the human neuroblastoma cell line, SH-SY5Y, we have identified an atRA-responsive gene (RAINB1: retinoic acid inducible in neuroblastoma cells) that is induced within 4 h after exposure of SH-SY5Y cells to atRA. RAINB1 mRNA is highly expressed in the nervous system (10.5- to 11-kb transcript) in both developing embryos and adults. Its expression is perturbed in developing rat embryos exposed to excess or insufficient atRA. RAINB1 is present on chromosome 11 and is spread over 38 exons, resulting in a putative ORF of 2,429 amino acids. The RAINB1 protein shows high similarity to a gene in Caenorhabditis elegans, unc-53, that is required for axonal elongation of mechanosensory neurons, suggesting that these proteins are orthologs. Thus, RAINB1 may represent a critical downstream gene in atRA-mediated neurite outgrowth.