Editorial overview: Protein–nucleic acid interactions: ‘Takes two to Tango’

This year we celebrate the 100th birthday of Rosalind Franklin; probably she would have not predicted the revolution that has taken place in structural biology for the last 5–7 years, but she would have been happy to witness it. The implementation of new technologies in cryo-electron microscopy (cryo-EM), especially the direct electron detectors, has brought atomic resolution structure determination of large, non-crystalline molecular assemblies into reach. In addition, significant improvements in sensitivity of nuclear magnetic resonance (NMR) spectrometers have allowed unravelling dynamic features of molecular assemblies of hundreds of kDa, a size range that had so far been out of reach for NMR.

The study of protein–nucleic acids interactions has taken good advantage of these new developments to unravel the mechanisms of key biological processes, even inside the cell, as recent work on the expressome has shown. Interactions between proteins and nucleic acids are key for life, as they control the central dogma of genetics, thereby determining when the cell replicates its genome and expresses a set of genes to respond to specific stimuli. To carry out this regulatory role, proteins can transitorily interact with nucleic acids, as in the assembly of replication complexes or in sequence-specific and general transcription factors, which recognize DNA target sites at initial steps of transcription to recruit RNA polymerases. Protein and nucleic acids also form stable complexes that undergo conformational changes during function. Some of these complexes are involved in gene regulation, such as the spliceosome, or work as nucleases or integrases in prokaryotic immunity, such as CRISPR-Cas complexes. Furthermore, specific proteins perform enzymatic functions that modify DNA to generate a new layer of regulation by epigenetic readers and writers; this additional regulation strategy is exploited also by RNA, for example by chemical modifications or controlled decay. The combination of high-resolution structural information of protein–nucleic acids complexes with single molecule approaches opens new possibilities to reveal the dynamic conformational landscape of these complexes and their transient interactions both in vitro and in situ.