A research group led by Prof. XUE Yuanchao from the Institute of Biophysics of the Chinese Academy of Sciences, systematically reviewed the development of RNA interactome technologies and analyzed the main advantages and technical limitations of different technologies, providing important guidance for the effective selection of tools for RNA functional research.

The results of their study were published in Molecular Cell on July 23.

The extensive transcription of the human genome generates a large number of non-coding RNA molecules that play a crucial role in the precise regulation of genetic information transmission such as transcription, splicing, and translation by interacting with other RNA molecules. Therefore, a comprehensive understanding of RNA-RNA interactions is key to deciphering the mechanisms of non-coding RNA function.

XUE and his team systematically outlined the development of RNA interactome technologies from in vitro to in vivo and to in situ, progressively improving the reliability of data. They introduced key principles used in various techniques for capturing and identifying RNA-RNA interactions such as chemical cross-linking, proximity ligation, and proximity barcoding.

The analysis of the main strengths and technical limitations of these techniques in identifying different types of RNA-RNA interactions will serve as an essential reference for the tool selection in RNA functional research.

Furthermore, the researchers also discussed the important conceptual advances brought by technological breakthroughs in RNA interactome research in areas such as RNA transcription regulation, cellular compartmentalization, and the pathogenic mechanism of viral infection.

They explored the challenges faced in further optimizing RNA interactome technologies, deciphering the interaction mechanisms of low-abundance RNA, and understanding the dynamic changes in RNA-RNA interactions.

The study holds significant guiding reference value for the analysis of RNA-RNA interactions and the study of non-coding RNA functional mechanisms, according to the researchers.

Fig. The function of RNA-RNA interaction. (Image by XUE Yuanchao's group)