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Alternative polyadenylation alters protein dosage by switching between intronic and 3'UTR sites.
de Prisco, Nicola; Ford, Caitlin; Elrod, Nathan D; Lee, Winston; Tang, Lauren C; Huang, Kai-Lieh; Lin, Ai; Ji, Ping; Jonnakuti, Venkata S; Boyle, Lia; Cabaj, Maximilian; Botta, Salvatore; Õunap, Katrin; Reinson, Karit; Wojcik, Monica H; Rosenfeld, Jill A; Bi, Weimin; Tveten, Kristian; Prescott, Trine; Gerstner, Thorsten; Schroeder, Audrey; Fong, Chin-To; George-Abraham, Jaya K; Buchanan, Catherine A; Hanson-Khan, Andrea; Bernstein, Jonathan A; Nella, Aikaterini A; Chung, Wendy K; Brandt, Vicky; Jovanovic, Marko; Targoff, Kimara L; Yalamanchili, Hari Krishna; Wagner, Eric J; Gennarino, Vincenzo A.
Afiliación
  • de Prisco N; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
  • Ford C; Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY, USA.
  • Elrod ND; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
  • Lee W; Department of Pediatrics, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
  • Tang LC; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, USA.
  • Huang KL; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
  • Lin A; Department Ophthalmology, Columbia University Irving Medical Center, New York, NY, USA.
  • Ji P; Department of Biological Sciences, Columbia University, New York, NY, USA.
  • Jonnakuti VS; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, USA.
  • Boyle L; Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
  • Cabaj M; Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, WC67+HC Dongcheng, Beijing, China.
  • Botta S; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, USA.
  • Õunap K; Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
  • Reinson K; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
  • Wojcik MH; Program in Quantitative and Computational Biology, Baylor College of Medicine, Houston, TX, USA.
  • Rosenfeld JA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA.
  • Bi W; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
  • Tveten K; Department of Pediatrics, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
  • Prescott T; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
  • Gerstner T; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
  • Schroeder A; Department of Translational Medical Science, University of Campania Luigi Vanvitelli, Caserta, Italy.
  • Fong CT; Department of Clinical Genetics, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.
  • George-Abraham JK; Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
  • Buchanan CA; Department of Clinical Genetics, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.
  • Hanson-Khan A; Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
  • Bernstein JA; Broad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Nella AA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • Chung WK; Baylor Genetics Laboratories, Houston, TX, USA.
  • Brandt V; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • Jovanovic M; Baylor Genetics Laboratories, Houston, TX, USA.
  • Targoff KL; Department of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.
  • Yalamanchili HK; Department of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.
  • Wagner EJ; Department of Child Neurology and Rehabilitation and Department of Pediatrics, Hospital of Southern Norway, Arendal, Norway.
  • Gennarino VA; Division of Medical Genetics, University of Rochester Medical Center, Rochester, NY, USA.
Sci Adv ; 9(7): eade4814, 2023 02 17.
Article en En | MEDLINE | ID: mdl-36800428
ABSTRACT
Alternative polyadenylation (APA) creates distinct transcripts from the same gene by cleaving the pre-mRNA at poly(A) sites that can lie within the 3' untranslated region (3'UTR), introns, or exons. Most studies focus on APA within the 3'UTR; however, here, we show that CPSF6 insufficiency alters protein levels and causes a developmental syndrome by deregulating APA throughout the transcript. In neonatal humans and zebrafish larvae, CPSF6 insufficiency shifts poly(A) site usage between the 3'UTR and internal sites in a pathway-specific manner. Genes associated with neuronal function undergo mostly intronic APA, reducing their expression, while genes associated with heart and skeletal function mostly undergo 3'UTR APA and are up-regulated. This suggests that, under healthy conditions, cells toggle between internal and 3'UTR APA to modulate protein expression.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Pez Cebra / Poliadenilación Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Pez Cebra / Poliadenilación Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article