1 research outputs found
Guanine nucleotide-binding protein-like 1 (GNL1) binds RNA G-quadruplex structures in genes associated with Parkinson鈥檚 disease
Abstract : 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鈥檚 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使 untranslated
regions (5使UTR) of mRNAs associated with Parkinson鈥檚 disease were demonstrated to in fact fold
in vitro by biochemical assays. Subcloning of the full-length 5使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