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.
mRNAs molecules carry information contained in genes to direct the formation of proteins. In specific circumstances, the cellular machinery modifies some mRNAs through the formation of m6A residues. To understand the function of these m6A marks, the authors used the yeast Saccharomyces cerevisiae in which their formation only occurs during meiosis that leads to spore formation.
Characterization of the Pho92 protein that specifically recognizes m6A residues revealed its importance for meiosis. m6A sites bound by Pho92 were identified and shown to be biologically functional. Unexpectedly, Pho92 was found to regulate an early step of meiosis by controlling DNA recombination. Overall, this study provides important clues on the role of m6A residues in mRNAs.
How many cell types are there in nature? How do they change during the lifecycle? These are two fundamental questions that researchers have been trying to understand in the area of biology. In this study, single-cell mRNA-sequencing data were used to profile over 2.6 million individual cells from mice, zebrafish, and Drosophila at different life stages, 1.3 million of which were newly collected. The comprehensive datasets allow investigators to construct a cross-species cell landscape that helps to reveal the conservation and diversity of cell taxonomies at genetic and regulatory levels. The resources in this study are assembled into a publicly available website at http://bis.zju.edu.cn/cellatlas/.
Continued expansion of the genetic code has required the use of synthetic tRNAs for decoding. Some of these synthetic tRNAs have unique structural features that are not observed in canonical tRNAs. Here, the authors applied single-molecule, biochemical and structural methods to determine whether these distinct features were deleterious for efficient protein translation on the ribosome. With a focus on selenocysteine insertion, the authors explored an allo-tRNA with a 9/3 acceptor domain. They observed a translational roadblock that occurred in A- to P-site tRNA translocation. This block was mediated by a tertiary interaction across the tRNA core, directing the variable arm position into an unfavorable conformation. A single-nucleotide mutation disrupted this interaction, providing flexibility in the variable arm and promoting efficient protein production.