Decoding subcellular spatial biology with high precision using RNA photocatalysts

RNA is a fundamental component of life.

Complex, dynamic, and spatial networks of molecular interactions between RNAs and other biomolecules are essential for maintaining cellular homeostasis.

Disruptions in the RNA interactome have been linked to a number of human diseases, implying that these molecular interactions could represent a new family of unexploited therapeutic targets.

Despite the growing appreciation of the importance of RNA, discovery, and characterization of RNA interactions at the transcriptome level is lagging behind, mainly due to the limitations of the existing methods including low precision, low throughput, low coverage, biased analysis, complicated protocols involving cumbersome biochemical fractionation or cell-line engineering.

With the present technology, many more years may pass before a comprehensive list of their functions, localizations, and interactions can be assembled, considering the immense size and complexity of the human transcriptome and RNA interactome.

This ERC project aims to establish a simple, versatile, and low-cost technology based-on photocatalytic proximity-labeling and the biRhoBAST aptamer for deciphering RNA-RNA and RNA-protein interactions with high precision for any given RNA at different resolutions, ranging from single-molecule to macromolecular complex level.

Owing to its innovative design, this technology will seamlessly integrate with advanced super-resolution RNA imaging techniques, providing valuable insights into the intricate interaction networks of RNA with high temporal and spatial resolution.

By applying this massively multiplexable technology to numerous biological settings and disease-related RNAs, we will expand our understanding of interactomes, uncover new insights into subcellular RNA structures and unravel fundamental molecular mechanisms of RNA diseases, leading to the discovery of novel functions for both RNA and proteins, and potentially unlocking new therapeutic targets.