Research articles

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.

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.

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.

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.

DNA polymerase μ 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 occurs without additional enzyme repositioning.

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.

Different kinases and phosphatases control the triggering of T-cell receptors. This signaling network is now reconstituted in vitro with CD3ζ, Lck, CD45, Csk and liposomes. Rigorous quantitative analyses reveal how the system is maintained in a quiescent state and how the kinase-phosphatase balance can be modulated by different events to allow activation in an ultrasensitive manner.

A long intergenic noncoding RNA, Firre, is now shown to localize to a domain across its own chromosomal locus and to distinct interacting transchromosomal loci in mouse and human cells. In addition, Firre interacts with nuclear-matrix factor hnRNPU. These results lead to a model in which Firre functions as a nuclear-organization factor modulating the topological organization of multiple chromosomes.

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.

A new study identifies the splicing factor SRSF6 as a proto-oncogene frequently overexpressed in human skin cancer. SRSF6-overexpressing mice develop skin hyperplasia and aberrant alternative splicing, with SRSF6 binding to alternative exons of the pre-mRNA of the extracellular-matrix protein tenascin C, thus promoting expression of isoforms characteristic of invasive and metastatic cancer.

Cancer cells often exhibit hyperactive signaling pathways. A new study now shows that Plcγ1 competes with Grb2 for binding to the fibroblast growth factor receptor 2 (FGFR2) in nonstimulated cells. Reduction in Grb2 expression results in increased Plcγ1 activity and cell motility, thus providing a molecular basis for the observation that reduced Grb2 expression correlates with metastatic potential.

The voltage-sensing domain (VSD) of voltage-gated ion channels transitions from a resting to an activated conformation upon membrane polarization. EPR spectroscopy analysis has now determined the position of the KvAP VSD in a resting conformation, revealing a new ‘tilt-shift’ model for transitioning between resting and activated states.

Transcription termination correlates with the loss of Tyr1 phosphorylation from the C-terminal domain (CTD) of Rpb1, an event thought to be necessary for the recruitment of termination factors. The phosphatase Glc7, an integral component of the cleavage-and-polyadenylation factor (CPF), is now shown to dephosphorylate Tyr1 and to contribute to termination in vivo.

Autorepression of PER-encoding genes underlies the periodic fluctuations in expression that drive the circadian clock. New work shows that histone deacetylase and histone methyltransferase activities are sequentially recruited to promoters of PER-encoding genes by separate PER protein–containing complexes and repress transcription via histone H3K9 modifications at those targets.

Some cancer cells lacking telomerase activity extend their telomeres via an alternative, recombination-based mechanism, termed ALT. A new study shows that depletion of histone chaperone ASF1 can induce ALT in both primary and cancer cells, suggesting that the ALT pathway may be triggered by changes in chromatin state.

Functional analyses of the ABC-F protein YjjK (EttA) suggest that it acts as a sensor of cellular energy and controls entry into the translational elongation cycle. Using cryo-EM and single-molecule FRET, EttA is shown to bind the ribosomal E site and engage both the L1 stalk and P-site tRNA to restrain ribosomal dynamics.

Although ABC-F proteins represent a ubiquitously distributed type of ATP-binding cassette (ABC) family member across phyla, their biological functions remain poorly characterized. A new study now shows that the bacterial ABC-F protein YjjK (EttA) gates ribosome entry into the translational cycle in an energy-dependent manner.