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Guanine Nucleotide-Binding Protein-Like 1 (GNL1) binds RNA G-quadruplex structures in genes associated with Parkinson's disease.
Turcotte, Marc-Antoine; Garant, Jean-Michel; Cossette-Roberge, Hélène; Perreault, Jean-Pierre.
Afiliação
  • Turcotte MA; Department of Biochemistry, Pavillon de Recherche Appliquée Sur le Cancer, Université de Sherbrooke, Sherbrooke, Québec, Canada.
  • Garant JM; Department of Biochemistry, Pavillon de Recherche Appliquée Sur le Cancer, Université de Sherbrooke, Sherbrooke, Québec, Canada.
  • Cossette-Roberge H; Department of Biochemistry, Pavillon de Recherche Appliquée Sur le Cancer, Université de Sherbrooke, Sherbrooke, Québec, Canada.
  • Perreault JP; Department of Biochemistry, Pavillon de Recherche Appliquée Sur le Cancer, Université de Sherbrooke, Sherbrooke, Québec, Canada.
RNA Biol ; 18(9): 1339-1353, 2021 09.
Article em En | MEDLINE | ID: mdl-33305682
RNAs are highly regulated at the post-transcriptional level in neurodegenerative diseases and just a few mutations can significantly affect the fate of neuronal cells. To date, the impact of G-quadruplex (G4) regulation in neurodegenerative diseases like Parkinson's disease (PD) has not been analysed. In this study, in silico potential G4s located in deregulated genes related to the nervous system were initially identified and were found to be significantly enriched. Several G4 sequences found in the 5' untranslated regions (5'UTR) of mRNAs associated with Parkinson's disease were demonstrated to in fact fold in vitro by biochemical assays. Subcloning of the full-length 5'UTRs of these candidates upstream of a luciferase reporter system led to the demonstration that the G4s of both Parkin RBR E3 Ubiquitin Protein Ligase (PRKN) and Vacuolar Protein Sorting-Associated Protein 35 (VPS35) significantly repressed the translation of both genes in SH-SY5Y cells. Subsequently, a strategy of using label-free RNA affinity purification assays with either of these two G4 sequences as bait isolated the Guanine Nucleotide-Binding Protein-Like 1 (GNL1). The latter was shown to have a higher affinity for the G4 sequences than for their mutated version. This study sheds light on new RNA G-quadruplexes located in genes dysregulated in Parkinson disease and a new G4-binding protein, GNL1.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Proteínas de Ligação ao GTP / Regiões 5' não Traduzidas / Proteínas de Transporte Vesicular / Ubiquitina-Proteína Ligases / Quadruplex G / Neuroblastoma Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Proteínas de Ligação ao GTP / Regiões 5' não Traduzidas / Proteínas de Transporte Vesicular / Ubiquitina-Proteína Ligases / Quadruplex G / Neuroblastoma Idioma: En Ano de publicação: 2021 Tipo de documento: Article