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In the classic central dogma, genetic information usually flows from DNA to RNA and is then expressed as proteins. However, in addition to the genetic code, nucleic acids also contain another layer of complex epigenetic modification systems dominated by chemical modifications to expand their information encoding capabilities. These modifications participate in a variety of important biological processes by regulating gene expression networks, also known as epigenetic modifications. Epigenetic modifications usually include chemical modifications to DNA, RNA, and proteins, and we refer to chemical modifications to DNA and RNA as nucleic acid modifications.
Nucleic acid modifications refer to the modification method of introducing additional chemical groups on DNA or RNA bases, which does not alter the arrangement of gene sequences but greatly improves the ability of bases to encode genetic information. More and more studies have shown that various DNA and RNA modifications actively participate in the regulation of various life processes, including embryonic development and organ differentiation. Dysregulation of these modifications has the potential to cause disease and even death in humans.
Each of the four bases of DNA has a different modification, with the 5-methylcytosine (5mC) modification being one of the most abundant. As an epigenetic marker, 5mC is closely linked to other chromatin factors and is involved in a wide range of developmental and physiological processes, even in human diseases, with a broad impact on gene expression.
N6 -methyl modification (6mA) is another important DNA modification and was initially thought to be the most prevalent DNA modification in bacteria, however, recent studies have found that it is also present in some eukaryotes at much lower levels than the proportion of modifications found in bacteria.
Among about 150 kinds of RNA modifications, m6A is the most abundant modification on mRNA and plays an important role in the regulation of gene expression. It is involved in multiple biological processes such as embryonic development, neuron regulation, and tumorigenesis.
Fig. 1 Diverse modifications on nucleic acids and their possible functions (Chen LQ, 2020)
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