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Dark DNA and stress (Review)

Int J Mol Med
. 2022 Dec 9;51(1):8. doi: 10.3892/ijmm.2022.5211

Konstantina Malliari 1Eleni Papakonstantinou 1Thanasis Mitsis 1Louis Papageorgiou 1Katerina Pierouli 1Io Diakou 1Konstantina Dragoumani 1Demetrios A Spandidos 2Flora Bacopoulou 3George P Chrousos 3Elias Eliopoulos 1Dimitrios Vlachakis 1,3,4,

“Dark DNA, the non-coding portion of the genome, constitutes ~98% of human DNA, while genomes of other large multicellular eukaryotes also appear to be mostly comprised of DNA that does not encode for proteins as well (1,2). New sequencing technologies made it possible to investigate this dark side of the genome, previously referred to as ‘junk’ (1). It appears that the extended DNA sequences of higher eukaryotic organisms that do not encode proteins are eventually transcribed in RNA to a very large percentage. Up to 80-90% of the genome of eukaryotic organisms is estimated to being transcribed, suggesting a potential role for such molecules (3). Furthermore, as the complexity of an organism increases, so does the percentage of dark DNA, while non-coding RNAs (ncRNAs) appear to dominate the regulation of its genome, in contrast to protein-coding genes (4).

Although the base-pair length and gene number appear to be very diverse between species, it appears that the amount of the non-coding regions of the genome of an organism is a sign of evolutional superiority. ncRNA molecules are able to orchestrate the expression of genetic information in the most complex, rapid and reversible manner, participating in almost every major biological process. A prime example of such a process is the maintenance of homeostasis, the internal physiological balance, despite internal and external stressful stimuli. These molecules have been shown to be excellent regulators of gene expression, with marked spatiotemporal specificity, rendering them ideal tools for regulating stress responses.”

Non-coding RNA (ncRNAs )have the potential to be used either as biomarkers or as therapeutic targets for disorders resulting from the loss of equilibrium, the disruption of homeostasis and the destabilization of the hypothalamic-pituitary-adrenal axis.”

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