The emergence of multidrug resistant bacteria is fuelled by diverse mobile genetic elements including genomic islands and conjugative plasmids that often carry many antibiotic resistance genes. Mobilizable genomic islands ('MGIs') such as Salmonella Genomic Island 1 (SGI1) confer resistance to a wide range of antibacterial agents, while IncC plasmids are large, broad-host-range, and globally distributed plasmids that contribute to the propagation of multidrug resistance genes. MGIs are usually thought of as relatively passive mobile genetic elements that await the arrival of a helper self-transmissible element (often a conjugative plasmid) for horizontal transfer. To accomplish this, MGIs need to excise from the host’s chromosome and be translocated through a pore encoded by their helper element. This study describes details of a genetic regulatory mechanism by which SGI1 actively associates itself with a conjugative lncC plasmid in order to undergo horizontal transfer.
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.
Ever since the discovery of microRNAs in C. elegans, their precise mechanism of action and the breadth of their biological impact has remained a matter of debate. Using a combination of unbiased proteomics, cell-free assays, genetics, and CRISPR/Cas9-based methods the authors identify the first direct effector of microRNA-directed translational repression in C. elegans, the novel GYF-domain protein GYF-1 and its partner IFE-4, and survey their physiological functions across several signature microRNA cascades using precisely engineered alleles and loci. The results provide a clear view of the importance of microRNA-directed translational repression in some, but not all microRNA cascades in C. elegans development, and unveil the surprising systems’ flexibility among microRNA’s silencing mechanisms. This discovery is of particularly high impact in that it provides exceptional new insight into the biological purposes of microRNAs in developmental and physiological contexts.
Formation of RNA-protein complexes often requires assisting factors in vivo. An example are UsnRNPs, the major building blocks of spliceosomes, whose formation depends on the Survival Motor Neuron (SMN) complex. In this study, an integrative structural biology approach was used to establish a comprehensive model of the SMN complex. Its core is formed by several copies of SMN arranged with alternating polarity. This creates a central platform onto which the Gemin6/7/8 module is recruited. SMN’s N-terminal parts extrude via flexible linkers from the core and enable binding of Gemin2 and UsnRNP proteins. Our data identify the SMN complex as a multivalent hub collecting UsnRNP proteins in its periphery to allow their joining with UsnRNA.
