RNA structure maps across mammalian cellular compartments.

Abstract

RNA structure is intimately connected to each step of gene expression. Recent advances have enabled transcriptome-wide maps of RNA secondary structure, termed RNA structuromes. However, previous whole-cell analyses lacked the resolution to unravel the landscape and also the regulatory mechanisms of RNA structural changes across subcellular compartments. Here we reveal the RNA structuromes in three compartments — chromatin, nucleoplasm and cytoplasm in human and mouse cells. The cytotopic structuromes substantially expand RNA structural information, and enable detailed investigation of the central role of RNA structure in linking transcription, translation, and RNA decay. We develop a resource to visualize the interplay of RNA-protein interactions, RNA modifications, and RNA structure, and predict both direct and indirect reader proteins of RNA modifications. We also validate a novel role of the RNA binding protein LIN28A as an N6-methyladenosine modification “anti-reader”. Our results highlight the dynamic nature of RNA structures and its functional significance in gene regulation.