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Review
. 2016 Jan 21;23(1):74-85.
doi: 10.1016/j.chembiol.2015.11.007.

Nucleic Acid Modifications in Regulation of Gene Expression

Kai Chen  1 , Boxuan Simen Zhao  1 , Chuan He  2
Affiliations
Review

Nucleic Acid Modifications in Regulation of Gene Expression

Kai Chen et al. Cell Chem Biol. .

Abstract

Nucleic acids carry a wide range of different chemical modifications. In contrast to previous views that these modifications are static and only play fine-tuning functions, recent research advances paint a much more dynamic picture. Nucleic acids carry diverse modifications and employ these chemical marks to exert essential or critical influences in a variety of cellular processes in eukaryotic organisms. This review covers several nucleic acid modifications that play important regulatory roles in biological systems, especially in regulation of gene expression: 5-methylcytosine (5mC) and its oxidative derivatives, and N(6)-methyladenine (6mA) in DNA; N(6)-methyladenosine (m(6)A), pseudouridine (Ψ), and 5-methylcytidine (m(5)C) in mRNA and long non-coding RNA. Modifications in other non-coding RNAs, such as tRNA, miRNA, and snRNA, are also briefly summarized. We provide brief historical perspective of the field, and highlight recent progress in identifying diverse nucleic acid modifications and exploring their functions in different organisms. Overall, we believe that work in this field will yield additional layers of both chemical and biological complexity as we continue to uncover functional consequences of known nucleic acid modifications and discover new ones.

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Figures

Figure 1
Figure 1
Scheme of the reversible cytosine methylation in DNA, and binding proteins that are known to or proposed to bind modified cytosine derivatives (Liyanage et al., 2014).
Figure 2
Figure 2
N6-methylation on adenine in genomic DNA. (A) A brief overview of biological function of methyl groups in bacterial genomic DNA. (B) High-throughput mapping of N6-methyladenine (6mA) in Chlamydomonas reinhardtii revealed a unique distribution pattern in the genome with complete depletion at transcription start sites (TSS) and high enrichment at the linker region between nucleosomes. (C) In Caenorhabditis elegans 6mA is installed by DAMT-1 and reversibly removed by NMAD-1. The “crosstalk” between 6mA and histone modification, particularly the histone H3 methylation, indicates critical roles that 6mA may play in gene expression regulation. (D) 6mA in Drosophila melanogaster could be converted back to A by Tet homolog DMAD. Intriguingly, the 6mA level is correlated with the expression level of transposon, supporting the regulatory significance of 6mA in eukaryotes.
Figure 3
Figure 3
N6-methyladenosine (m6A) in mRNA and its biological significance. The reversible methylation and demethylation process occurs in the nucleus, catalyzed by methyltransferase complex and demethylases, respectively. The m6A modification has profound effects on mRNA fate: it switches mRNA to active translation mode, and also accelerates its decay rate.
Figure 4
Figure 4
A partial spectrum of diverse RNA chemical modifications.
See this image and copyright information in PMC

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