NAR’s Breakthrough Articles present high-impact studies answering long-standing questions in the field of nucleic acids research and/or opening up new areas and mechanistic hypotheses for investigation. These articles are chosen by the Editors on the recommendation of Editorial Board Members and Referees. Articles are accompanied by a brief synopsis explaining the findings of the paper and where they fit in the broader context of nucleic acids research. They represent the very best papers published at NAR.
mRNA 3’ processing is a critical mechanism for gene regulation. Over 70% of human genes have multiple sites of polyadenylation, which are thought to significantly impact gene regulation. However, much remains to be learned about how poly(A) sites are recognized and how their selection is regulated. A prevalent model in the field is that mRNA 3’ processing and its regulation are carried out exclusively by proteins. In this study, the authors describe experiments that implicate snoRNAs as potential important regulators of mRNA 3’ processing. In vitro and in vivo assays provide evidence that snoRNAs are associated with the human mRNA 3’ processing complexes and play important roles in regulating poly(A) site recognition. The study provides mechanistic insights based on both in vitro studies of individual poly(A) sites and global analyses of polyadenylation profiles. The results support a competitive inhibitor model, which is a new mechanism for mRNA 3’ processing regulation.
Features of genomic organization in a nucleotide-resolution molecular model of the Escherichia coli chromosome
"The challenge that modeling a chromosome represents is substantial: the E. coli chromosome, for example, includes over 4.6 million base pairs (Mb) of DNA, with a contour length of 1.6 mm compressed into a cell less than 3 μm in length in a predictable orientation". In this study, the authors describe structural models of entire E. coli chromosomes at resolutions of one nucleotide per bead (1NTB) confined within the experimentally determined volume of the nucleoid. The study employs a novel multi-scale methodology that integrates a whole range of experimental data, and shows the central importance of transcription and supercoiling in bacterial chromosome structure.
This study reveals that a novel antibacterial toxin from Yersinia kristensenii shares a common structural fold with RNase A and possesses the superfamily's characteristic ribonuclease activity. Homologs of this toxin are associated with diverse secretion systems in both Gram-negative and Gram-positive bacteria, suggesting that RNase A-like toxins are commonly deployed in inter-bacterial competition. Contact-dependent growth inhibition (CDI) is a toxin-delivery platform that is distributed widely amongst proteobacteria and is particularly common in pathogens. There is substantial functional and structural diversity observed between CDI toxin/immunity protein pairs, and these systems are important mediators of inter-cellular competition and self/nonself recognition in bacteria. Antibacterial toxin secretion systems are ubiquitous in nature and are beginning to inspire the development of “next generation” antimicrobial therapies.