Despite highly effective antiretroviral therapies, the human immunodeficiency virus (HIV-1) remains a major public health threat. Its pathogenesis depends on its ability to establish a persistent infection in cells of the immune system. Our study highlights a new insight into how HIV-1 evades early restriction by the immune system. We showed that 2'O-methylation marks found inside HIV-1 RNA promote viral evasion from the antiviral action of the interferon-stimulated gene 20-kDa protein (ISG20), an innate immune restriction factor with a nuclease activity. By disrupting the level of 2'O-methylation of the HIV-1 genome, we demonstrated that ISG20 impairs the reverse transcription process of hypomethylated viruses, as a result of viral RNA decay.
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.
Site-specific DNA recombinases alter DNA connectivity by recognizing specific DNA sequences, cutting the DNA strands and pasting them together in a new configuration. Such enzymes play a variety of biological roles and are useful biotechnology tools. The simplest site-specific recombination systems recombine any two cognate sites regardless of context. Others have evolved elaborate mechanisms to ensure that only one of multiple possible recombination products is produced. Tn3 resolvase will cut and reconnect two target sequences only if they lie on the same DNA molecule, and if they are in the proper relative orientation. This study presents new structural and biochemical data that lead to a new model of the large protein-DNA complex formed by Tn3 resolvase and its cognate sites. This 3D model illustrates how DNA topology can be harnessed to regulate the activity of a recombinase and provides a basis for engineering Tn3 resolvase and related recombination systems as genome editing tool ...
This article describes a strategy for single cell RNA sequencing that avoids the usual imitation required by first physically compartmentalizing single cells. Based on the slow rate of mRNA diffusion relative to mRNA capture on beads, the authors devised a method that profiles single cell mRNA among a multiple cell population, within one reaction mixture, termed "Onepot-Seq". This approach uses a time-constrained, transient reaction chamber that forms around each cell, with only slow diffusion of the cell contents after gentle lysis. The sparse distribution of cells and beads allows the beads to capture the profile of a single cell with minimal intercellular mRNA contamination.
