Discovery and Accurate Detection of Rare Nucleic Acid Modifications

Abstract Nucleic acid modifications play essential roles in diverse biological processes, ranging from gene expression regulation to stress response. While traditional research focused on common modifications like methylation, recent discoveries are unveiling a wide range of rare modifications with potentially crucial functions. However, accurately detecting and mapping these modifications pose significant challenges due to their low abundance and diverse chemical properties. This article summarizes the recent discoveries of rare DNA and RNA modifications across various organisms, highlighting their potential biological significance. Furthermore, it critically evaluates the limitations of current mapping techniques, including potential sources of false positives and negatives. Finally, the article discusses emerging strategies for overcoming these challenges and future opportunities in the field of rare nucleic acid modification detection.