RNA structure probing dash seq

Abstract

RNA constitutes the central conduit for information storage, conveyance, and manipulation in biological systems (1, 2). RNAs encode their critical information at two levels. First, the primary sequence directs protein synthesis and contains simple cis-acting elements that bind regulatory factors and other RNAs. Second, most RNAs fold to create complex base-paired and higher order structures with intrinsic regulatory functions. Until recently, it has been difficult or impossible to interrogate the structures of most RNAs, especially in complex biological environments. Ongoing advances in nucleotide-resolution RNA structure probing have made possible increasingly rigorous and quantitative analyses (3), and recent large-scale and whole-genome studies have revealed or better defined rules for how RNA structure regulates translation initiation, protein folding, splicing, and access to protein binding sites (4–6). The clear power of next-generation sequencing (NGS) to transform nucleic acid-based analyses (7, 8) has motivated significant efforts (a scientific dash) to meld chemical and enzymatic probing experiments with NGS readouts (termed seq experiments). The melding of RNA structure probing experiments with NGS readout is a potential marriage made in transcriptome heaven. Two papers in PNAS (9, 10) illustrate important progress toward this highly sought goal.