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òòò½Íø– Researchers from A*STAR’s Genome Institute of òòò½Íø(GIS) have found an innovative approach to sequencing single-cell ribonucleic acid (RNA) to study the roles of RNA structure in individual cells. As RNA shapes in individual cells can vary and drive different functions, studying the collective RNA shapes in many cells may overlook the individual variability in both RNA structure and function.  

Named Sc-SPORT for Single Cell Structure Probing Of RNA Transcripts, this new approach is able to identify biomarkers crucial for human development and disease, based on shape rather than sequence. While single-cell gene expression analysis has shown the extent of diversity that is present in seemingly similar individual cells, it was unclear whether other elements could also influence cell fate. Through this approach, researchers can now use RNA structure as an additional level of information to identify cell types in development and diseases. 

In the past decade, understanding different components in individual cells through diverse single-cell sequencing technologies have progressed by leaps and bounds. As researchers delve deeper into the layers of individual cells, predicting cellular trajectories become increasingly accurate. 

Led by A*STAR’s GIS Deputy Executive Director and Principal Investigator, Dr Wan Yue and A*STAR’s GIS fellow Dr Jiaxu Wang, in collaboration with Dr Roland Huber, Principal Investigator, A*STAR’s Bioinformatics Institute (BII), this study marks the first exploration of RNA structure at a single-cell level, specifically targeting rare cell types and RNA structure heterogeneity. In the past, when studying the structure of RNA in large quantities, researchers required millions of cells to begin. Such an approach led to a generic overview, combining all the shapes from all the cells, which made it hard to see the specific differences in RNA structure among individual cells. Now, by performing RNA structure probing in single cells, researchers can better appreciate the information present in each cell and identify when the cells could go wrong.  

The study of RNA structure in single cells opens doors to identifying structure biomarkers in individual cells that can be dysregulated in disease, adding an additional layer of information to existing single-cell information. This RNA structure could serve as a novel biomarker or drug target for diseases whereby the RNA levels do not change. It would enable researchers to identify cell types based on RNA structure in addition to RNA expression and better understand how RNA viruses can fold in individual cells. Currently, the team is optimising scale-up approaches for single-cell RNA structure sequencing and applying this approach to more complex cell developmental process and cancer.