Inefficient splicing of overlapping viral transcripts can lead to intermolecular dsRNA formation. During wildtype virus infection the presence of the E1B55K/E4orf6 viral hijacked ubiquitin ligase leads to the ubiquitination of cellular RNA binding proteins (RBPs) RALY and hnRNPC, which precludes their binding to viral RNA. In the presence of RALY and hnRNPC viral transcripts are poorly spliced, leading to the formation of dsRNA between the exonic regions of viral RNAs to the intronic regions of transcripts derived from the opposing strand. After these dsRNA molecules form, a fraction of the cytoplasmic dsRNA-sensor PKR translocates into the nucleus, where it co-localizes with viral dsRNA and is activated by auto-phosphorylation.
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.
Genomic DNA replication requires replisome assembly, in which parental double-stranded DNA (dsDNA) is unwound by helicases into single-stranded DNA (ssDNA). DNA polymerases then synthesize nascent strands. The replisome assembly mechanism in archaea is still poorly understood. In particular, the mechanism by which archaeal replicative polymerases are coordinated with corresponding helicase factors remains unclear. Here, the investigators demonstrate the molecular basis for archaeal replisome assembly, including an atomic structure of the DP1N–Gins51C–GAN ternary complex, which is believed to act as the replisome core in the model archaeon T. kodakarensis. A structural comparison of comparable regions within the archaeal and yeast replisomes revealed that the structural basis for the interaction between their polymerases and the replicative helicase is conserved in two domains of life. These findings provide insight into the archaeal replisome assembly and helicase activation.
Viruses that infect bacteria (bacteriophages) are everywhere life is found. These deadly molecular machines inject DNA into their bacterial hosts, instructing them to make more bacteriophages. As a defense, bacteria evolved "molecular scissors"– enzymes that can snip invading DNA and stop the infection. The authors have now determined the pathways by which some bacteriophages fight back to evade their hosts' defenses. Their work shows that enzymes encoded by bacteriophages catalyze the attachment of amino acids and other molecules to DNA. These modifications act as a shield against the molecular scissors making the DNA resistant to cleavage. Since amino acids normally function in proteins, this result is surprising and suggests a chemical diversity of modifications on A,G,C and T that awaits further exploration. The bacteriophage DNA modifying enzymes discovered in this study might one day be harnessed to anchor DNA on chips, label DNA with fluorescent dyes and much more.
