Articles in 2014

The long elusive mammalian meiosis-specific kinetochore factor has been identified in mice; MEIKIN—which plays an equivalent role to the yeast proteins Spo13 and Moa1—ensures mono-orientation, protects sister chromatid cohesion and recruits the kinase PLK1 to the kinetochores.

The full complement of transcriptional regulators that affect synthesis of the plant secondary cell wall remains largely undetermined; here, the network of protein–DNA interactions controlling secondary cell wall synthesis of Arabidopsis thaliana is determined, showing that gene expression is regulated by a series of feed-forward loops to ensure that the secondary cell wall is deposited at the right time and in the right place.

Highly substituted carbon–carbon bonds are constructed using a simple iron catalyst and an inexpensive silane: more than 60 examples of this reaction — in which heteroatom-substituted olefins are reacted with electron-deficient olefins — are presented.

This study describes a fast, clathrin-independent endocytic pathway mediated by endophilin, dynamin and actin; the pathway is activated by ligand binding to a variety of cargo receptors, and endophilin-mediated endocytosis occurs primarily at the leading edges of cells where lamellipodin and the lipid PtdIns(3,4)P₂ ensure endophilin targeting.

Polycomb group proteins are known to maintain gene repression during development; however, when autism susceptibility candidate 2 (AUTS2) associates with some Polycomb group complexes, these complexes have an unexpected gene activation role, offering new insight into the role of AUTS2 in neurological disorders.

Using electron cryomicroscopy, the structure of the closed-state rabbit ryanodine receptor RyR1 in complex with its modulator FKBP12 is solved at 3.8 Å; in addition to determining structural details of the ion-conducting channel domain, three previously uncharacterized domains help to reveal a molecular scaffold that allows long-range allosteric regulation of channel activities.

The CRISPR-Cas9 system, a powerful tool for genome editing, has been engineered to activate endogenous gene transcription specifically and potently on a genome-wide scale and applied to a large-scale gain-of-function screen for studying melanoma drug resistance.

This study presents an extensive molecular characterization of the reprograming process by analysis of transcriptomic, epigenomic and proteomic data sets describing the routes to pluripotency; it finds distinct routes towards two stable pluripotent states characterized by distinct epigenetic events.

This study tracks dragonfly head and body movements during high-velocity and high-precision prey-capture flights, and shows that the dragonfly uses predictive internal models and reactive control to build an interception trajectory that complies with biomechanical constraints.

The forced expression of key transcription factors can induce somatic cells to acquire pluripotency characteristics; here high levels of reprogramming factors are used to induce mouse embryonic fibroblasts to a stable alternative pluripotent state with low intercellular adhesion.

Here the structure of the membrane protein complex sodium-translocating NADH:quinone oxidoreductase (Na⁺-NQR) is described; as Na⁺-NQR is a component of the respiratory chain of various bacteria, including pathogenic ones, this structure may serve as the basis for the development of new antibiotics.

The African Genome Variation Project contains the whole-genome sequences of 320 individuals and dense genotypes on 1,481 individuals from sub-Saharan Africa; it enables the design and interpretation of genomic studies, with implications for finding disease loci and clues to human origins.

A study of freely moving bats provides new insights into how the brain encodes a three-dimensional neural compass; neurons were identified encoding the three Euler rotation angles of the head (azimuth, pitch, and roll) and recordings from these head-direction cells revealed a toroidal model of spatial orientation mapped out by cells tuned to two circular variables (azimuth × pitch).

This study uses single-cell expression profiling of pluripotent stem cells after various perturbations, and uncovers a high degree of variability that can be inherited through cell divisions—modulating microRNA or external signalling pathways induces a ground state with reduced gene expression heterogeneity and a distinct chromatin profile.

Using electron cryomicroscopy, the closed-state structure of rabbit RyR1 is determined at 4.8 Å resolution; analysis confirms that the RyR1 architecture consists of a six-transmembrane ion channel with a cytosolic α-solenoid scaffold, and suggests a mechanism for Ca²⁺-induced channel opening.

Using electron cryomicroscopy, the structure of the rabbit RyR1 calcium channel is determined at 6.1 Å resolution in the closed state and 8.5 Å in the open state, revealing how calcium binding to the EF-hand of RyR1 regulates channel opening and facilitates calcium-induced calcium release.

As part of the mouse ENCODE project, genome-wide transcription factor (TF) occupancy repertoires and co-association patterns in mice and humans are studied; many aspects are conserved but the extent to which orthologous DNA segments are bound by TFs in mice and humans varies both among TFs and genomic location, and TF-occupied sequences whose occupancy is conserved tend to be pleiotropic and enriched for single nucleotide variants with known regulatory potential.

Atomic resolution crystal structures of influenza A and B polymerases are presented; comparison of these structures provides mechanistic insight into influenza polymerase functions, explaining the processes of cap-snatching and cap-dependent priming, which are unique to segmented negative-strand RNA viruses.

Mouse genomic footprinting reveals conservation of transcription factor (TF) recognition repertoires and trans-regulatory circuitry despite massive turnover of DNA elements that contact TFs in vivo.

The Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types; these data were compared with those from human to confirm substantial conservation in the newly annotated potential functional sequences and to reveal pronounced divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.