Étude de protéines liant les G-quadruplexes situés en 5’UTR de gènes impliqués dans la maladie de Parkinson
Bibliographic record
Abstract
Within the nervous system, the post-transcriptional regulatory mechanisms contribute to the different cellular phenotypes. Indeed, weak deregulations can lead to diseases. RNA G-quadruplexes (G4) are emerging as new players in post-transcriptional regulation. G4s are very stable secondary structures found in DNA and RNA. They are formed by a minimum of two tetrads of guanines and stabilized by monovalent cations usually potassium. At the RNA level, they are involved in different mechanisms, such as alternative polyadenylation, alternative splicing, activation and inhibition of translation, and maturation of microRNAs. According to many, G4s are seen as events rather than entities. Trans elements, like proteins, are able to ensure their folding and unfolding. A bioinformatic analysis confirmed that there is indeed an enrichment of RNA G4s in the transcripts of the nervous system. This analysis also identified Parkinson's disease as one of the diseases with the highest proportion of potential G4 (pG4). Out of 16 disease-related genes, 15 of them contain a least one pG4. Then, different biochemical techniques such as fluorescence assay, circular dichroism, and in-line probing were used to confirm the formation of G4s located in the different 5’ untranslated regions (5’UTR). These techniques identified 4 new RNA G4s that have never been characterized before. Subsequently, luciferase assays concluded that two of these G4s, in the mRNA of VPS35 and PRKN, have a repressive effect on translation. The proteins capable of binding these two G4s were then identified by mass spectrometry. The protein Guanine Nucleotide-Binding Protein-Like 1 (GNL1) was identified as being a protein capable of binding the two G4s. Finally, the interaction between GNL1 and the G4 from VPS35 and PRKN was confirmed by electrophoretic mobility shift assays. In brief, this study identified a new protein, GNL1, which can bind two new G-quadruplexes located in deregulated genes associated with Parkinson's disease. The regulation of the interaction between GNL1 and the two G4s could be a therapeutic option to counter the deregulations present in Parkinson's disease.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".