Volume 23 Issue 5, May 2016

The sirtuin family protein SIRT6 is a stress-responsive NAD-dependent histone deacetylase with key roles in glucose homeostasis, DNA repair and cellular lifespan. SIRT6 is now shown to mediate deacetylation of histone H3 Lys18 specifically at pericentric chromatin, thus maintaining transcriptional silencing of satellite repeats in a manner independent of HP1 and trimethylated H3 Lys9, thereby assuring correct segregation of chromosomes.

Translation elongation entails a one-codon movement of the mRNA–tRNA complex along the mRNA and is catalyzed by the forward translocase EF-G. The structurally related back-translocase EF4 catalyzes movement in the opposite direction when the ribosome stalls, but its physiological role in mammals had been unknown. Genetic ablation of EF4 in mice is now found to cause testis-specific mitochondrial deficiency and impaired spermatogenesis.

Brown fat has a tremendous capacity to oxidize fatty acids and generate heat, owing to the presence of an 'uncoupling protein', UCP1. The fatty acids themselves are understood to activate UCP1, but Chouchani et al. now propose that oxidation of a critical cysteine residue on UCP1 is additionally required to sensitize the protein to fatty acids.

Two new studies of the CRISPR nuclease Cpf1 reveal the structural and catalytic flexibility of this leaner, meaner alternative to Cas9.

The fundamental mechanics of how EF-G catalyzes translocation of the mRNA and tRNA pairs on the ribosome has been intensely studied for over three decades. Two kinetic studies now reveal the sequence of events and the timing of key conformational changes in the ribosome during translocation and identify new intermediates in this complex process.

The synaptonemal complex (SC) connects homologous chromosomes in meiotic prophase, thus promoting genetic exchange and ensuring accurate chromosomal segregation at anaphase. In this Review, the authors discuss the structural organization of the SC and how its assembly, maintenance and disassembly are regulated in yeast and metazoans.

Structural and functional analyses of a new family of tick-derived C5 inhibitors in complex with inhibitor OmCI and therapeutic antibody eculizumab reveal diverse mechanisms for inhibition and provide insight into C5 activation by C5 convertases.

B-cell translocation gene-4 (Btg4) bridges interactions of translation initiation factor eIF4E and CCR4–NOT deadenylase, thus triggering decay of maternal mRNA during mouse oocyte maturation.

SELEX selections and crystallographic analyses have allowed development of a DNA aptamer that inhibits autotaxin with high potency and specificity, and exhibits efficacy against bleomycin-induced pulmonary fibrosis in model mice.

High-resolution kinetic analysis and enzyme trapping assays reveal how PCNA coordinates 5′-flap generation and processing by Pol δ and FEN1 during Okazaki-fragment maturation.

α-synuclein amyloid fibrils are associated with Parkinson's disease. SSNMR analyses now reveal the atomic structure of a pathogenic human α-synuclein fibril, providing a framework for understanding fibril nucleation, propagation and interactions with small molecules.

The CARD-only protein INCA inhibits inflammasome assembly by capping caspase-1 CARD oligomers and preventing their further polymerization.

Crystal structures of the human ADAR2 deaminase domain in complex with RNA duplexes reveal the mechanisms for ADAR2's action and explain its substrate preference. The work also provides a rationale to understand disease-related mutations.

The sirtuin family protein SIRT6 maintains pericentric heterochromatin silencing at human centromeres through deacetylation of a newly discovered substrate, H3K18, thus protecting cells against mitotic errors, genomic instability and cellular senescence.

Genetic ablation of EF4 in mice leads to male sterility due to mitochondrial translation defects, which can be compensated for in somatic tissues by mTOR-mediated upregulation of cytoplasmic translation.

RNA interference constrains antisense lncRNA transcriptomes, and its loss during budding yeast evolution is associated with an increase in genome-wide expression of antisense lncRNAs.

The crystal structure of the C-terminal region of Zika virus nonstructural protein 1 (NS1) reveals a fold similar to those of other flaviviruses (dengue and West Nile viruses) but different surface electrostatic features.

An analysis of previously published data on fiber formation by sickle-cell hemoglobin reveals a universal curve when delay time is plotted against supersaturation (ratio of protein concentration to solubility).