Advances in RNA secondary structure prediction and RNA modifications: Methods, data, and applications

Abstract: Due to the hierarchical organization of RNA structures and their pivotal roles in fulfilling RNA functions, the formation of RNA secondary structure critically influences many biological processes and has thus been a crucial research topic. This review sets out to explore the computational prediction of RNA secondary structure and its connections to RNA modifications, which have emerged as an active domain in recent years. We first examine the progression of RNA secondary structure prediction methodology, focusing on a set of representative works categorized into thermodynamic, comparative, machine learning, and hybrid approaches. Next, we survey the advances in RNA modifications and computational methods for identifying RNA modifications, focusing on the prominent modification types. Subsequently, we highlight the interplay between RNA modifications and secondary structures, emphasizing how modifications such as m6A dynamically affect RNA folding and vice versa. In addition, we also review relevant data sources and provide a discussion of current challenges and opportunities in the field. Ultimately, we hope our review will be able to serve as a cornerstone to aid in the development of innovative methods for this emerging topic and foster therapeutic applications in the future.