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Two studies provide insights into the distinct strategies used by prokaryotes and eukaryotes to pause translation in order to facilitate cotranslational targeting of membrane proteins to the translocon.
Two complementary papers demonstrate that the homologous type II transmembrane proteins LAP1 and LULL1 adopt nucleotide-free AAA+ ATPase folds and donate arginine fingers to complete the active sites of Torsin AAA+ ATPases. Activated Torsin complexes appear to function in nuclear and endoplasmic reticulum membrane-remodeling processes, including a nuclear vesiculation pathway that carries large cellular and viral cargoes from the nucleus into the cytoplasm.
cIAP1 undergoes a dramatic conformational change during activation that is now shown to be due to the dynamic and metastable nature of the closed form of the enzyme. The discovery of such a striking mechanism for functional control was enabled by state-of-the-art enzymological and biophysical methods.
The Seventh International Conference on the Hsp90 Chaperone Machine took place in October 2014, in Seeon, Germany. The program highlighted recent findings in a variety of areas, including structures of heat-shock protein 90 (Hsp90)–client protein complexes, coordination of Hsp90 with cochaperones, new cellular and physiological roles for Hsp90 and therapeutic targeting of the Hsp90 ensemble for the treatment of disease and prevention of infection.
The fate of an mRNA is regulated by internal base modifications that generate the modified nucleotides N6-methyladenosine, 5-methylcytosine and inosine. Three new studies show that yeast and human mRNAs also contain pseudouridine residues and that pseudouridylation is induced in various stress states, hinting at a new pathway for post-transcriptional control of mRNA.
The human histone macroH2A.1.1 recruits activated PARP1 enzyme to chromatin through its poly(ADP-ribose)-binding macrodomain. New work shows that PARP1 and CBP can be displaced from chromatin in cancer cells that have lost macroH2A.1.1, thus leading to changes in histone H2B acetylation at cancer-relevant genes.
Emerging evidence from genome-wide analyses reveals that DNA methylation, an epigenetic modification associated with the repression of gene expression, can also promote transcriptional activation.
Yeast cells display synchronized oscillation between phases of high and low oxygen consumption accompanied by a program of cyclical gene expression. A study monitoring mRNA levels, histone modifications and chromatin occupancy of histone modifiers during the yeast metabolic cycle (YMC) at high temporal resolution reveals both 'just-in-time' supply of YMC gene products and new patterns of chromatin reconfiguration associated with transcriptional regulation.
After being used in the 1950s to treat morning sickness in pregnant women, with devastating effects, thalidomide and its derivatives (lenalidomide and pomalidomide) are now widely used in cancer therapy. New structural work from two groups gives insights into the basis for the teratogenicity and other clinical effects of these drugs.
Recent structural progress on prokaryotic and eukaryotic Argonaute proteins is reviewed here, along with the insights obtained into guide and target binding and target cleavage. Comprehensive phylogenetic analyses lead to a map of Argonaute's evolutionary paths, relating structural features and physiological roles.
The development of new strategies to deplete maternal histone proteins in vivo and in vitro has led to the discovery of unexpected roles of histones in forming a functional nuclear envelope.
Classical PUF proteins bind to single-stranded RNA with sequence specificity that can be engineered by site-directed mutagenesis according to a simple RNA-recognition code. Now in-depth probing of the PUF RNA-recognition code enhances future design of PUF proteins and exposes hidden complexity in generating specificity.
Mechanisms of DNA damage repair within actively transcribed genes are poorly understood. Five new reports shed light on the contributions of chromatin to this process by uncovering roles for histone H3 Lys36 methylation, a post-translational modification previously linked to transcription elongation, in the control of DNA-damage signaling and double strand break repair.
Two sibling DNA polymerases synthesize most of the eukaryotic nuclear genome. A new study provides insights into the distinct protein interactions that deliver these replicases for asymmetric leading- and lagging-strand replication and reveals possible cross-talk between DNA replication and other cellular processes.
Post-transcriptional mRNA regulation is often attained by lengthening or shortening the 3′ poly(A) tail of a transcript. Eukaryotic mRNAs show a spectrum of deadenylation rates, thus allowing intricate control of gene expression, but the mechanisms that determine such rates are unclear. Three new studies highlight the structural and biochemical features of a key enzyme in removing poly(A) tails, the PAN2–PAN3 complex, providing clues to how different mRNA deadenylation rates can be achieved.
Traditionally, maintenance of gene silencing by the Polycomb group proteins has been thought to involve recruitment of Polycomb repressive complex (PRC) 1 by PRC2-mediated trimethylation of K27 on histone H3. Three recent studies challenge this model by demonstrating that monoubiquitination of histone H2A, which is catalyzed by PRC1 complexes, can recruit PRC2 and potentiate its catalytic activity.
ATP is continuously synthesized inside mitochondria and exported to the cytoplasm via transporter and channel proteins residing in the inner and outer mitochondrial membranes, respectively. In this issue of Nature Structural & Molecular Biology, a new crystal structure of the mitochondrial channel protein VDAC-1 provides the basis for a detailed simulation study that unravels the mechanism by which ATP diffuses across the outer mitochondrial membrane at a fast rate.
New high-resolution structures of microtubules reveal that GTP and taxol each stimulate microtubule assembly by inducing straight protofilaments and promoting extension of the interdimer spacing. However, these effects take place through different mechanisms: GTP directly extends loops around the active site, whereas taxol works like a remote lever.
X-ray structural analysis of spliceosomal U6 small nuclear RNA bound to Prp24 reveals a complex interlocked RNA–protein assembly and suggests models for key steps in spliceosome assembly and recycling.
