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RNA pull-down confocal nanoscanning (RP-CONA) detects quercetin as pri-miR-7/HuR interaction inhibitor that decreases α-synuclein levels.
Zhu, Siran; Choudhury, Nila Roy; Rooney, Saul; Pham, Nhan T; Koszela, Joanna; Kelly, David; Spanos, Christos; Rappsilber, Juri; Auer, Manfred; Michlewski, Gracjan.
Afiliação
  • Zhu S; Infection Medicine, University of Edinburgh, The Chancellor's Building, Edinburgh EH16 4SB, UK.
  • Choudhury NR; Dioscuri Centre for RNA-Protein Interactions in Human Health and Disease, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.
  • Rooney S; Infection Medicine, University of Edinburgh, The Chancellor's Building, Edinburgh EH16 4SB, UK.
  • Pham NT; Infection Medicine, University of Edinburgh, The Chancellor's Building, Edinburgh EH16 4SB, UK.
  • Koszela J; School of Biological Sciences, IQB3, University of Edinburgh, Edinburgh EH9 9FF, UK.
  • Kelly D; School of Biological Sciences, IQB3, University of Edinburgh, Edinburgh EH9 9FF, UK.
  • Spanos C; The Wellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK.
  • Rappsilber J; The Wellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK.
  • Auer M; The Wellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK.
  • Michlewski G; Department of Biotechnology, Technische Universität Berlin, Berlin 13355, Germany.
Nucleic Acids Res ; 49(11): 6456-6473, 2021 06 21.
Article em En | MEDLINE | ID: mdl-34107032
RNA-protein interactions are central to all gene expression processes and contribute to a variety of human diseases. Therapeutic approaches targeting RNA-protein interactions have shown promising effects on some diseases that are previously regarded as 'incurable'. Here, we developed a fluorescent on-bead screening platform, RNA Pull-Down COnfocal NAnoscanning (RP-CONA), to identify RNA-protein interaction modulators in eukaryotic cell extracts. Using RP-CONA, we identified small molecules that disrupt the interaction between HuR, an inhibitor of brain-enriched miR-7 biogenesis, and the conserved terminal loop of pri-miR-7-1. Importantly, miR-7's primary target is an mRNA of α-synuclein, which contributes to the aetiology of Parkinson's disease. Our method identified a natural product quercetin as a molecule able to upregulate cellular miR-7 levels and downregulate the expression of α-synuclein. This opens up new therapeutic avenues towards treatment of Parkinson's disease as well as provides a novel methodology to search for modulators of RNA-protein interaction.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Quercetina / MicroRNAs / Alfa-Sinucleína / Proteína Semelhante a ELAV 1 Limite: Humans Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Quercetina / MicroRNAs / Alfa-Sinucleína / Proteína Semelhante a ELAV 1 Limite: Humans Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2021 Tipo de documento: Article