Recent technical advances in the study of nucleic acid modifications

• Published in: Molecular cell Vol. 81; no. 20; pp. 4116 - 4136
• Main Authors: Owens, Michael C., Zhang, Celia, Liu, Kathy Fange
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.10.2021
• Subjects: 5-methylcytidine; Adenosine - analogs & derivatives; Adenosine - metabolism; Animals; Cytidine - analogs & derivatives; Cytidine - metabolism; DNA - genetics; DNA - metabolism; DNA Methylation; DNA modification; Epigenesis, Genetic; Genetic Techniques; Humans; inosine; Inosine - metabolism; N4-acetylcytidine; N6-methyladenosine; pseudouridine; Pseudouridine - metabolism; RNA - genetics; RNA - metabolism; RNA modification; RNA Processing, Post-Transcriptional; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA modification; inosine; N4-acetylcytidine; DNA modification; N6-methyladenosine; pseudouridine; 5-methylcytidine; N-methyladenosine; N-acetylcytidine
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2021.07.036

Enzyme-mediated chemical modifications of nucleic acids are indispensable regulators of gene expression. Our understanding of the biochemistry and biological significance of these modifications has largely been driven by an ever-evolving landscape of technologies that enable accurate detection, mapping, and manipulation of these marks. Here we provide a summary of recent technical advances in the study of nucleic acid modifications with a focus on techniques that allow accurate detection and mapping of these modifications. For each modification discussed (N6-methyladenosine, 5-methylcytidine, inosine, pseudouridine, and N4-acetylcytidine), we begin by introducing the “gold standard” technique for its mapping and detection, followed by a discussion of techniques developed to address any shortcomings of the gold standard. By highlighting the commonalities and differences of these techniques, we hope to provide a perspective on the current state of the field and to lay out a guideline for development of future technologies. In this review, Owens et al. provide summaries and critiques of some classic and cutting-edge techniques for detection of nucleic acid modifications. By drawing comparisons between techniques for study of several different modifications, they highlight the underlying principles future methods can utilize.