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.
Animal cells are complex and contain different regions. These regions may require different strategies for controlling gene expression. Rosenthal and co-workers suggest that enzymes can act in a region-specific manner to control gene expression in neurons. This work provides a new model for considering how function is directed to locations with cells.
By combining single-molecule tracking, single-cell protein quantitation, quantitative kinetic analysis, and genetic engineering, the authors have made novel discoveries on how the behavior of a metal-responsive transcription regulator in live bacterial cells challenges two long-standing mechanistic paradigms in regulator-DNA interactions.
The identity and methylation status of the first transcribed nucleotide in eukaryotic mRNA 5′ cap modulates protein expression in living cells
Using in vitro generated capped mRNA, the influence of the first transcribed nucleotide and its methylation status on translation was systematically studied. Translation rates were found to depend strongly on the identity of the nucleotide and its methylation, mRNA purity and the immune state of the cell. These findings are of broad interest both in terms of describing potential strategies to improve expression of exogenous proteins (for applications such as gene therapies) while also providing considerable new insights in the mechanisms of regulation of mRNA translation.