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The Upstream 1350~1250 Nucleotide Sequences of the Human ENDOU-1 Gene Contain Critical Cis-Elements Responsible for Upregulating Its Transcription during ER Stress.
Lee, Hung-Chieh; Chao, Hsuan-Te; Lee, Selina Yi-Hsuan; Lin, Cheng-Yung; Tsai, Huai-Jen.
Afiliación
  • Lee HC; Department of Life Science, Fu-Jen Catholic University, New Taipei City 242062, Taiwan.
  • Chao HT; Department of Life Science, Fu-Jen Catholic University, New Taipei City 242062, Taiwan.
  • Lee SY; Faculty of Sciences and Engineering, Maastricht University, 6211 LK Maastricht, The Netherlands.
  • Lin CY; Institute of Biomedical Sciences, Mackay Medical College, New Taipei City 25245, Taiwan.
  • Tsai HJ; Department of Life Science, Fu-Jen Catholic University, New Taipei City 242062, Taiwan.
Int J Mol Sci ; 24(24)2023 Dec 12.
Article en En | MEDLINE | ID: mdl-38139221
ABSTRACT
ENDOU-1 encodes an endoribonuclease that overcomes the inhibitory upstream open reading frame (uORF)-trap at 5'-untranslated region (UTR) of the CHOP transcript, allowing the downstream coding sequence of CHOP be translated during endoplasmic reticulum (ER) stress. However, transcriptional control of ENDOU-1 remains enigmatic. To address this, we cloned an upstream 2.1 kb (-2055~+77 bp) of human ENDOU-1 (pE2.1p) fused with reporter luciferase (luc) cDNA. The promoter strength driven by pE2.1p was significantly upregulated in both pE2.1p-transfected cells and pE2.1p-injected zebrafish embryos treated with stress inducers. Comparing the luc activities driven by pE2.1p and -1125~+77 (pE1.2p) segments, we revealed that cis-elements located at the -2055~-1125 segment might play a critical role in ENDOU-1 upregulation during ER stress. Since bioinformatics analysis predicted many cis-elements clustered at the -1850~-1250, we further deconstructed this segment to generate pE2.1p-based derivatives lacking -1850~-1750, -1749~-1650, -1649~-1486, -1485~-1350 or -1350~-1250 segments. Quantification of promoter activities driven by these five internal deletion plasmids suggested a repressor binding element within the -1649~-1486 and an activator binding element within the -1350~-1250. Since luc activities driven by the -1649~-1486 were not significantly different between normal and stress conditions, we herein propose that the stress-inducible activator bound at the -1350~-1250 segment makes a major contribution to the increased expression of human ENDOU-1 upon ER stresses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Endorribonucleasas Específicas de Uridilato Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Endorribonucleasas Específicas de Uridilato Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza