Scientists at Stockholm University and SciLifeLab have achieved a groundbreaking feat by creating the first technique capable of unveiling the specific functions that microRNAs carry out within individual cells.
This represents a significant advancement compared to current state-of-the-art methods, which demand millions of cells. Importantly, this breakthrough will empower researchers to investigate microRNAs in intricate tissues like the brain for the very first time.
Their remarkable study has been published in the prestigious journal Nature Biotechnology.
MicroRNAs are tiny molecules that play a crucial role in controlling gene activity by binding to and breaking down the RNAs produced by those genes. It is noteworthy that over 60% of all human genes are thought to be regulated by microRNAs. Consequently, it is not surprising that these small molecules are involved in numerous biological processes, including diseases like cancer.
To understand the function of a specific microRNA, it is essential to determine precisely which RNAs it targets. While methods for achieving this do exist, they typically necessitate a substantial amount of material, often on the order of millions of cells, to be effective.
Researchers at Stockholm University and SciLifeLab have introduced an innovative technique for identifying microRNA targets at the single-cell level. These cells are incredibly tiny, with a diameter around one-hundredth of a millimeter and a weight less than a billionth of a gram. Yet, they form the fundamental building blocks of living organisms.
With this highly sensitive method, researchers can track the interactions between microRNAs and thousands of RNAs within individual cells during biological processes such as the cell cycle or the development of red blood cells. Intriguingly, their findings reveal that microRNAs have distinct roles in each cell, even within the same process.
In the future, this method can also be applied to study microRNA interactions in entire tissues, offering insights into the precise activities of the various cell types that make up complex organs like the brain.
In our research team, we want to understand and ultimately make mathematical models of gene regulation at the level of the single cell. Our new method is a huge leap towards making this possible”.
Marc Friedländer, Associate Professor, Stockholm University
Dr. Inna Biryukova played a pivotal role in leading the development of the laboratory method, while the bulk of the advanced computational analyses were carried out by Ph.D. Student Vaishnovi Sekar. Their combined efforts were instrumental in the success of this research project.
In terms of complexity of the computational work, this is uncharted territory, and we lacked reference points and thresholds. We had to explore a myriad of approaches to devise a methodology that not only works but also yields biologically meaningful observations.”
Vaishnovi Sekar, PhD Student, Stockholm University
Sekar, V., et al. (2023). Detection of transcriptome-wide microRNA–target interactions in single cells with agoTRIBE. Nature Biotechnology. doi.org/10.1038/s41587-023-01951-0.