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Using Akron-seq, a novel approach that captures native 3′ and 5′ ends of capped and polyadenylated RNAs, Mourelatos and colleagues show that mRNAs are subject to repeated cotranslational endonucleolytic cuts at the ribosome exit channel.
Although mechanisms wherein pre-existing H3K27 methylation directs recruitment of PRC2 to support its own maintenance have been proposed, H3K27 methylation patterns in mESCs are not dependent on self-autonomous epigenetic inheritance.
The structure of the minimal GTPase domain of human MFN1 reveals a new, closed conformation and suggests how mitofusin pulls membranes closer to facilitate fusion and how MFN2 mutations impair mitochondria in Charcot–Marie–Tooth neuropathy type 2A.
Structural analyses of Xenopus tropicalis TRPV4 reveal a single ion-binding site in the selectivity filter and distinct interactions between the voltage-sensor-like and pore domains and provide a blueprint to understanding disease-related mutations.
p63 activation in response to DNA damage leads to oocyte death and loss of fertility in women receiving chemotherapy. Activation requires sequential phosphorylation by CHK2 and CK1 kinases, and inhibition of these kinases rescues oocytes from apoptosis induced by chemotherapy.
A platform for high-throughput expression screening and large-scale production of cystine-dense peptides, alongside a global structure-based classification, is presented.
RNA-directed miRNA degradation triggered by a brain-specific genome-encoded transcript regulates explorative and anxiety-like behavior in zebrafish and affects balance and motor learning in mice.
2′-O-methylation within mRNA coding regions sterically perturbs interactions of ribosomal-monitoring bases with cognate codon–anticodon helices, leading to excessive rejection of cognate aminoacylated tRNAs during initial selection and proofreading.
Crystal structures of human GPT in complex with tunicamycin provide insight into mechanisms of inhibition and differences between human and bacterial enzymes, leading to the design of an analog with specificity for the bacterial enzyme.
In vivo, in vitro and in silico experiments demonstrate that interface residues of homomeric proteins are enriched toward protein C termini to avoid premature assembly and aggregation.
Cryo-ET analyses of the microtubule-bound mouse dynein–dynactin complex reveal two dimeric dyneins interacting with the dynactin–cargo adaptor complex, a configuration that can account for processivity and directionality of dynein transport activity.
The X-ray structures of engineered variants of the human serotonin transporter show that the antidepressants sertraline, fluvoxamine and paroxetine occupy the central substrate-binding site and stabilize the transporter in an outward-open conformation.
Cryo-EM analyses of human PRC2 bound to dinucleosomes with one unmodified (substrate) and one H3K27me3-containing (activating) nucleosome support a model for H3K27me3-based PRC2 activation and spreading.
An NMR structure of Thermus thermophilus membrane electron transporter CcdA in an oxidized, outward-facing state suggests an elevator-type mechanism shuttles reactive cysteines to relay reducing equivalents across the membrane.
In vitro and cellular assays unexpectedly reveal that shelterin protein TRF2 binds TERRA and stimulates strand invasion within telomere repeats and that TRF1 suppresses this activity to prevent telomere loss and genome instability.
The structure of the fully assembled yeast exocyst complex, which mediates the tethering of secretory vesicles to the plasma membrane during exocytosis, provides new insights to hierarchical complex assembly and the mechanism of vesicle tethering.
During oogenesis, H3K4 trimethylation is targeted to genomic elements through transcription-dependent and transcription-independent mechanisms, the latter relying on MLL2 recruitment to unmethylated CpG-rich regions.
The cryo-EM structure of the full-length TRPV5 channel in complex with inhibitor econazole reveals a domain-swapped architecture and provides insights into mechanisms of inhibition.
The ER-resident Hsp70 BiP is regulated by NEF Bap. The interactions between BiP and Bap are now dissected using biochemistry, molecular modeling and smFRET approaches, revealing that Bap affects both domains of BiP, to coordinate release of substrate and nucleotide.
Nucleotide exchange factors (NEFs) trigger substrate release from molecular chaperone Hsp70. The authors found that armadillo-type NEFs (yeast Fes1, human HspBP1) competitively prevent rebinding of released substrate.