- Sağlık Bilimlerinde İleri Araştırmalar Dergisi
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- THE FREQUENCY AND FITNESS OF m6A-ASSOCIATED VARIANTS COULD BE MODULATED BY THE THERMODYNAMIC STABILI...
THE FREQUENCY AND FITNESS OF m6A-ASSOCIATED VARIANTS COULD BE MODULATED BY THE THERMODYNAMIC STABILITY OF AN OVERLAPPING G-QUADRUPLEX
Authors : Çağrı Güleç
Pages : 219-228
Doi:10.26650/JARHS2023-1349345
View : 31 | Download : 45
Publication Date : 2023-10-24
Article Type : Research
Abstract :Objective: Post-transcriptional modifications like m6A (N6-methyladenosine) and secondary structures like G-quadruplex (G4) are formations that play a vital role in RNA processing. Their synergy also has functional consequences. Since m6A is known to be enzymatically created in the DRACH-motif, and that genetic variants can create a novel DRACH-motif or abolish a pre-existing DRACH-motif, we can hypothesize that variants which affect the gene product level through modulating m6A-G4 colocalization, may also consequently affect fitness and change the allele frequency. To test this hypothesis, the rare and common variants in selected human genes were investigated to determine their effect on DRACH-G4 colocalization. Material and Methods: Genomic sequences and variant information were retrieved from the GRCh37/hg19 and Biomart-Ensembl databases. Experimentally determined G4 sequences were obtained from two different studies. Results: Common variants leading to the formation of a novel DRACHmotif were found to be significantly higher inside the G4 structure than outside. In contrast, rare variants with the same feature were higher outside the G4-structure and had uneven distribution alongside the premRNA. The uneven distribution of the DRACH-creating rare variants was observed to correlate with their effect on thermodynamic stability of the overlapping G4. Conclusion: Selective DRACH-G4 colocalization suggests that m6A is evolutionally favorable when overlapping with G4. The thermodynamic stability could lead to uneven distribution of DRACH-G4 colocalization, favorable in 3-prime-side, but not in 5-prime-side. We can conclude that the fitness, and consequently frequency of a DRACH-creating variant is prone to become higher or lower depending in its position and effect on the overlapping-G4 stability.Keywords : RNA modifikasyonu, N6-metiladenozin, G-kuadrupleks, alel sıklığı