Structural switch from a multistranded G-quadruplex to single strands as a consequence of point mutation in the promoter of the human <i>GRIN1</i> gene
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Bibliographic record
Abstract
Abstract A huge number of G-rich sequences forming quadruplexes are found in the human genome, especially in telomeric regions, UTRs, and the promoter regions of a number of genes. One such gene is GRIN1 encoding the NR1 subunit of the N-methyl-d-aspartate receptor (NMDA). Several lines of reports have implicated that attenuated function of NMDA results in schizophrenia, a genetic disorder characterized by hallucinations, delusions, and psychosis. Involvement of the GRIN1 gene in the pathogenesis of schizophrenia has been extensively analysed. Recent reports have demonstrated that polymorphism in the promoter region of GRIN1 at position −855 (G/C) has a possible association with schizophrenia. The binding site for the NF-κB transcription factor gets altered due to this mutation, resulting in reduced gene expression as well as NMDA activity. By combining gel electrophoresis (PAGE), circular dichroism (CD) and CD melting techniques, the G → C single nucleotide polymorphism (SNP) at the G-rich sequence (d-CTTAGCCCGAGGAG̲GGGGGTCCCAAGT; GRIN1) was investigated. We report that the GRIN1 sequence can form an octameric/multistranded quadruplex structure with parallel conformation in the presence of K+ as well as Na+. CD and gel studies are in good correlation in order to detect molecularity and strand conformation. The parallel G-quadruplex species was hypothesized to be octameric in K+/Na+ salts. The mutated sequence (d-CTTAGCCCGAGGAC̲GGGGGTCCCAAGT; GRIN1M) remained single stranded under physiological conditions. CD melting studies support the formation of an interstranded G-quadruplex structure by the GRIN1 sequence. Two structural models are propounded for a multistranded parallel G-quadruplex conformation which might be responsible for regulating the gene expression normally underlying memory and learning.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 it