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.
The ability to modulate translation capacity, which resides greatly on a number of ribosomes, provides robustness in fluctuating environments. Because translation is energetically the most expensive process in cells, cells must constantly adapt the rate of ribosome production to resource availability. This is primarily achieved by regulating ribosomal RNA (rRNA) synthesis, to which ribosomal proteins synthesis is adjusted. The multiplicity of rRNA encoding operons per bacterial genome exceeds requirements for the maximal growth rates in non-stress conditions. In this study, the authors provide evidence that a major function of rRNA operon multiplicity is to ensure that individual operons are not saturated by RNA polymerases during adaptation to environmental fluctuations, which can result in catastrophic chromosome replication failure and cell death.
Extended pluripotent stem cells (EPSCs), which can form both embryonic and extraembryonic lineages, have important application prospect in regenerative medicine. However, the epigenetic regulation in EPSCs remains unclear. In this study, we demonstrated that EPSCs have the uniquely epigenetic signature compared with ESCs and discovered that Yin Yang-1 (YY1) acting as a key regulator could safeguard EPSC extended pluripotency by controlling epigenetic crosstalk among DNA methylation, histone modification and high-order chromatin structure. Moreover, YY1 is required for the in vitro derivation of extraembryonic endoderm (XEN)-like cells from EPSCs. Together, this study highlights the importance of a YY1-DNA methylation-chromatin loops-histone modification axis in regulating EPSC identity and development potentials.
Riboswitches have challenged our understanding of biological regulation for almost two decades. The ability of small molecules to bind to RNA and control gene expression offers another layer of regulation and the potential for direct action by compounds in the environment. While some riboswitches have been well studied, we lack a general understanding of how changes in RNA structure switch genetic expression from “On” to “Off”. In this study, the authors propose an elegant “strand displacement” model to explain how the RNA structure shifts between “On” and “Off” states as the concentration of small molecule ligand changes. These observations help us to understand how riboswitches enable genetic decision-making. The data provide a possible general mechanism for understanding how the competition between different strand displacement outcomes can influence RNA folding. Understanding RNA folding pathways could advance the successful design of drugs that target RNA.