RNA Structure in Cells

Long noncoding RNAs, lncRNAs, are important regulators of gene expression, but their structural features are largely unknown. Published in PNAS, the Weeks and Calabrese, Pharmacology, labs used structure-selective chemical probing to examine the structure of the Xist lncRNA in living cells.

Xist is the essential RNA that turns off gene expression in one of the two X chromosomes in all female mammals. The research groups made the remarkable observation that the Xist RNA adopts well-defined and complex structures throughout its entire 18-kb length. By looking for changes in reactivity induced by the cellular environment, they were able to identify numerous previously unknown hubs of protein interaction.

This work represents a transformative advance in understanding structure–function relationships in all lncRNAs, which are encoded by a larger fraction of the human genome than are proteins.