Regulation of a novel isoform of Receptor Expression Enhancing Protein REEP6 in rod photoreceptors by bZIP transcription factor NRL

Hao, H., Veleri, S., Sun, B., Kim, D.S., Keeley, P.W., Kim, J.W., Yang, H.J., Yadav, S.P., Manjunath, S.H., Sood, R., Liu, P., Reese, B.E., Swaroop, A.
Human molecular genetics   23(16): 4260-71 (Journal)
Registered Authors
Liu, Pu Paul, Sood, Raman
immunoprecipitation, chromatin, retinal cone, dna, complementary, enhancer elements, genetic, exons, genes, introns, tissue membrane, protein isoforms, racial group, rod photoreceptors, transfection, zebrafish, mice, retina, basic-leucine zipper transcription factors
MeSH Terms
  • Animals
  • Basic-Leucine Zipper Transcription Factors/genetics*
  • Basic-Leucine Zipper Transcription Factors/metabolism
  • Enhancer Elements, Genetic
  • Eye Proteins/genetics*
  • Eye Proteins/metabolism
  • Gene Regulatory Networks
  • HEK293 Cells
  • Humans
  • Introns
  • Membrane Transport Proteins/chemistry*
  • Membrane Transport Proteins/genetics
  • Membrane Transport Proteins/metabolism
  • Mice, Inbred C57BL
  • Organ Specificity
  • Protein Isoforms/genetics*
  • Protein Isoforms/metabolism
  • Retinal Rod Photoreceptor Cells/metabolism*
  • Transcriptional Activation*
  • Zebrafish
24691551 Full text @ Hum. Mol. Genet.
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.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes