BAP-seq – bioorthogonal masked acylating agents for proximity-dependent RNA labelling

The localization of RNA plays a crucial role, dictating cell physiology in a context-dependent manner. Yet, despite its importance, methods for unbiased mapping of RNA within cells have been scarce and less robust compared to protein mapping techniques. However, a groundbreaking study has now introduced a powerful new approach that promises to shed light on the spatial organization of RNA within cells.

Researchers at the University of Chicago have developed novel chemical probes known as α-alkoxy thioenol and chloroenol esters, which act as potent acylating agents when unmasked under controlled conditions. These probes are paired with the localized expression of a bioorthogonal esterase—a specialized enzyme that can selectively activate the probes within specific cellular locales. This innovative combination gives rise to a groundbreaking platform called BAP-seq, short for bioorthogonal acylating agents for proximity labelling and sequencing.

Using this cutting-edge technique, researchers can selectively unmask the enol probes in areas of interest within the cell, allowing them to map the distribution of RNA in various cellular compartments, including membrane-bound and membrane-less organelles. By precisely pinpointing the locations of RNA molecules, scientists can gain unprecedented insights into the spatial organization of cellular processes.

What makes this approach particularly powerful is its ability to provide spatial information about RNA distribution with high resolution and specificity. Unlike previous methods, which often lacked precision and reliability, BAP-seq offers a robust and comprehensive way to interrogate the cellular organization of RNAs.

The implications of this breakthrough are far-reaching. By unraveling the spatial organization of RNA within cells, researchers can better understand how cells function under normal conditions and how dysregulation of RNA localization may contribute to disease states. Furthermore, the ability to map RNA distribution with such precision opens up new avenues for exploring the intricate machinery of cellular life.

The development of BAP-seq represents a significant advancement in the field of RNA biology. With its ability to uncover the hidden world of RNA within cells, this innovative technique promises to revolutionize our understanding of cellular organization and function, paving the way for new discoveries in biology and medicine.

Pani S, Qiu T, Kentala K et al. (2024) Bioorthogonal masked acylating agents for proximity-dependent RNA labelling. Nat Chem [Epub ahead of print]. [article]

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