|Nature Structural aamp; Molecular Biology - Issue - nature.com science feeds|
Long noncoding RNAs (lncRNAs) have divergent roles in the nuclei of higher eukaryotes, including chromatin modification and regulation of nuclear bodies. A new study adds a new lncRNA function to the current list: serving as a platform for trans-chromosomal associations. At least three gene loci located on different chromosomes are brought together around the transcription site of a lncRNA termed functional intergenic repeating RNA element (Firre).
Enhancers are cis-regulatory elements that enable precise spatiotemporal patterns of gene expression during development and are notable for their ability to function at large distances from their target genes. This Review discusses classic enhancer studies, placing these in the context of recent studies that confirm the role of enhancers in orchestrating gene expression during development and their significance in disease pathogenesis.
Rpn11, the only essential deubiquitinase (DUB) of the 26S proteasome, sits at the top of the substrate entry pathway and facilitates substrate degradation through cotranslocational deubiquitination. The structure of the Rpn11–Rpn8 complex, together with functional assays, offers insight into Rpn11's promiscuous DUB activity during proteasomal degradation.
Secretory proteins are translocated across the endoplasmic reticulum cotranslationally, in association with the ribosome–Sec61 translocon complex. Using a small domain in which tertiary structure can be reversibly controlled, a new study now demonstrates that folding of the nascent peptide within the compartment near the ribosome exit vestibule can influence translocation outcome.
Centromeric chromatin is established largely by epigenetic processes and involves the incorporation of histone H3 variant CENP-A. A new study implicates monoubiquitinated histone H2B (H2Bub1) in maintaining active centromeric chromatin in human cells and in fission yeast. H2Bub1 prevents heterochromatin formation at centromeres and promotes noncoding transcription, centromere integrity and accurate chromosomal segregation.
Voltage sensor domains (VSDs) transducer changes in the electrical field across cell membranes into conformational changes that alter the activation state of an effector domain. Structural and biophysical data on the VSD from Ci-VSP reveal the first view of this domain in the resting state, providing new insight into voltage-dependent structural transitions.
DNA polymeraseμ promotes nonhomologous end joining (NHEJ) of DNA double-strand breaks. Crystal structures of truncated human DNA polymerase μ with and without a gapped DNA substrate provide the first structural evidence that the loop 1 domain is repositioned to permit template binding and that catalysis occurswithout additional enzyme repositioning.
The 'dissolvasome', composed of TopIIIα, BLM and RMI proteins, coordinates DNA-helicase and DNA-topoisomerase activities to resolve double Holliday junctions (dHJs) generated during DNA recombination and repair. The first crystal structure of a human TopIIIα–Rmi1 subcomplex provides insights into how topoisomerase is stimulated to promote dHJ decatenation.
Bacteria use alternative sigma factors to direct transcription initiation from new sets of gene promoters in response to environmental stress. Complementary structural and biochemical analyses now reveal a new promoter-recognition mechanism that is the basis for the altered promoter specificity conferred by stress-responsive sigma factors.
The crystal structure of human RXRα–LXRβ heterodimer bound to its cognate DNA element, with agonists and a coactivator peptide, is now solved. The heterodimer shows an X-shaped organization, with DNA-binding and ligand-binding domains crossed, in contrast to previous crystal structures of nuclear receptor complexes.
Enterovirus HEV71 is responsible for recurring epidemics in developing countries. New structural analyses coupled with in silico docking methods have allowed for the generation of potent inhibitors of viral-envelope uncoating that block subsequent insertion of viral RNA into the host cell.
|Nature Structural aamp; Molecular Biology - AOP - nature.com science feeds|
Resection of DNA double strand–break ends generates single strands that can spontaneously anneal to undergo mutagenic microhomology-mediated end joining (MMEJ). A combination of genetic and biophysical assays now shows that replication protein A (RPA) thwarts strand annealing by binding to the resected ends to promote Rad51 filament assembly and error-free repair by homologous recombination.
A new study reports the first structure of a retrotransposon reverse transcriptase in complex with its cognate polypurine tract RNA-DNA hybrid. In contrast to its retroviral counterparts, Ty3 reverse transcriptase forms an asymmetric homodimer that forms in the presence of substrate, with its RNase H and DNA polymerase activities likely contributed by separate subunits.
IRSp53 is a BAR-domain protein under the control of Rho family GTPases and has crucial roles in processes such as cell motility and tumor invasiveness. In a new study, IRSp53 is shown to be autoinhibited and is synergistically activated by the combinatorial action of Cdc42 and the tumor-promoting factor Eps8.
Structural and functional analysis reveal the resting state of the voltage-gated proton channel Hv1. Comparison with structures of voltage-sensing domains from other systems, captured in the activated state, will aid in understanding the mechanism of voltage sensing.