The ability to characterize RNA folding and structure is therefore essential to advance our understanding of the diverse functions of RNA. Moreover, it has been reported that mutations disrupting RNA structures can be associated with human diseases such as repeat expansion disorders, retinoblastoma and breast cancer 6. These diverse functions, are based on the ability of single-stranded RNA molecules to fold into diverse secondary and tertiary structures 4, 5. However, this view has been changed since the discoveries that RNA can function as catalytic ribozymes, as temperature-sensing and metabolite-sensing riboswitches, and as epigenetically regulatory long noncoding RNAs (lncRNAs), among others 1, 2, 3. RNA was once conceptualized as a passive passenger for the delivery of genetic information recorded in DNA to the functional products-proteins.

Ultimately, we hope the technological advances will deepen our understanding of RNA biology and facilitate RNA structure-based biomedical research such as designing specific RNA structures for therapeutics and deploying RNA-targeting small-molecule drugs. Finally, we provide our thoughts on the latest advances and challenges in RNA structure determination methods, as well as on future directions for both experimental approaches and artificial intelligence-based computational tools to model RNA structure. We also highlight how the rapid increase of experimental data facilitates the integrative modeling approaches for better resolving RNA structures.

Here, we summarize the state-of-the-art experimental and computational technologies developed to evaluate RNA secondary and tertiary structures. Therefore, accurately determining RNA structure is integral to advancing our understanding of RNA functions. Most of these activities depend on RNAs’ specific structures. Beyond transferring genetic information, RNAs are molecules with diverse functions that include catalyzing biochemical reactions and regulating gene expression.

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