title: Regulation of a novel isoform of Receptor Expression Enhancing Protein REEP6 in rod photoreceptors by bZIP transcription factor NRL.
abstract: The Maf-family leucine zipper transcription factor NRL is essential for rod photoreceptor development and functional maintenance in the mammalian retina. Mutations in NRL are associated with human retinopathies, and loss of Nrl in mice leads to a cone-only retina with the complete absence of rods. Among the highly down-regulated genes in the Nrl(-/-) retina, we identified receptor expression enhancing protein 6 (Reep6), which encodes a member of a family of proteins involved in shaping of membrane tubules and transport of G-protein coupled receptors. Here, we demonstrate the expression of a novel Reep6 isoform (termed Reep6.1) in the retina by exon-specific Taqman assay and rapid analysis of complementary deoxyribonucleic acid (cDNA) ends (5'-RACE). The REEP6.1 protein includes 27 additional amino acids encoded by exon 5 and is specifically expressed in rod photoreceptors of developing and mature retina. Chromatin immunoprecipitation assay identified NRL binding within the Reep6 intron 1. Reporter assays in cultured cells and transfections in retinal explants mapped an intronic enhancer sequence that mediated NRL-directed Reep6.1 expression. We also demonstrate that knockdown of Reep6 in mouse and zebrafish resulted in death of retinal cells. Our studies implicate REEP6.1 as a key functional target of NRL-centered transcriptional regulatory network in rod photoreceptors.
authors.affiliation: Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Hao
authors.affiliation: Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Shobi
authors.initials: S
authors.lastname: Veleri
authors.affiliation: Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA, USA.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Neuroscience Research Institute Department of Molecular, Cellular and Developmental Biology and.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Keeley
authors.affiliation: Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jung-Woong
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Sharda P
authors.initials: SP
authors.lastname: Yadav
authors.affiliation: Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Souparnika H
authors.initials: SH
authors.lastname: Manjunath
authors.affiliation: Oncogenesis and Development Section and Zebrafish Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Raman
authors.initials: R
authors.lastname: Sood
authors.affiliation: Oncogenesis and Development Section and Zebrafish Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Liu
authors.affiliation: Neuroscience Research Institute Department of Psychological and Brain Sciences, University of California at Santa Barbara, CA, USA.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Reese
authors.affiliation: Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA swaroopa@nei.nih.gov.
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D053263:Gene Regulatory Networks; D057809:HEK293 Cells; D006801:Humans; D007438:Introns; D008565:Membrane Proteins; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D015533:Transcriptional Activation; D015027:Zebrafish
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D005136:Eye Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C084884:Nrl protein, mouse; D020033:Protein Isoforms; C000602312:REEP6 protein, mouse