Research articles

Lysakovskaia et al. use a multiomics approach to investigate promoter-proximal termination of RNA polymerase II and show that it is a regulated process that can contribute to both upregulation and downregulation of genes during a human cell type transition event.

Here the authors present deep quantitative glycoprofiling (DQGlyco), a method that enables high-throughput analysis of protein glycosylation dynamics. Using DQGlyco, they link gut microbiome composition to brain glycoproteins and provide insights into glycoform functionality and tissue specificity.

The authors elucidate how the complex of mannosidase Mnl1 and protein disulfide isomerase (Pdi1) initiates endoplasmic-reticulum-associated protein degradation (ERAD). Mnl1 demannosylates misfolded, globular proteins and Pdi1 then reduces the disulfides to generate unfolded proteins competent for ERAD.

Cryo-EM structures of circularly permuted group II introns determined at 2.5- to 2.9-Å resolutions reveal dynamic D6, unexpected interactions and metal ions for catalysis, which elucidate conserved mechanisms of back-splicing to generate circular RNAs.

Here, the authors report the structure of the nicotinamide adenine dinucleotide phosphate dehydrogenase–photosystem I–light-harvesting complex I supercomplex, providing insights into subunit interactions and the role of cofactors.

Using in vitro reconstitution experiments with purified components, the authors show that five interacting ciliary tip proteins collectively form cork-like structures at microtubule tips and make microtubule growth very slow and processive.

The structure of a spontaneously activated immune protein is determined by cryo-electron microscopy. This reveals the passage of an entire domain through a transient opening. The authors investigate the mechanism by multiple biophysical approaches.

Cryo-EM reveals how transthyretin moves, offering insights into ligand binding and amyloidogenesis. The work highlights the utility of cryo-EM in studying small proteins and uncovering targets for structure-based drug design in transthyretin amyloidosis.

Here, the authors map X-chromosome activity during female mouse germ cell reprogramming, revealing gradual, region-specific gene reactivation. Some genes resist reactivation, retaining epigenetic memory, offering insights into female germline epigenetics.

Using complementary cryo-electron microscopy and functional studies, the authors demonstrate that botulinum neurotoxins exploit the accompanying nontoxic bacterial proteins, OrfXs and P47, activated by host digestive proteases, to greatly enhance their oral toxicity.

Here, the authors provide insights into a splicing quality control mechanism. The Gpl1–Gih35 complex binds to the active site of aberrant spliceosomes, blocks splicing progression and triggers the spliceosome discard pathway.

This study reveals how anamorelin, a superagonist targeting the ghrelin receptor, works compared to other drugs. Structural insights into ligand binding and genetic variations offer a framework for personalized therapies

Gong, Reynolds et al. use cryo-electron microscopy and cryo-electron tomography to uncover how the actin cross-linking factor fascin uses structural flexibility to assemble helical actin filaments into symmetry-mismatched hexagonal bundles.

LYCHOS is a lysosome-localized cholesterol sensor involved in mTORC1 activity regulation. Here, the authors report the three-dimensional structure of LYCHOS bound to cholesterols, revealing the recognition mechanism for this molecule.

Tao et al. show that epidermal growth factor receptor and insulin-like growth factor 1 receptor activation enhances thymidine kinase 1 expression through ERK phosphorylation and deubiquitylation mediated by ubiquitin carboxyl-terminal hydrolase 9X, thus enhancing enzyme activity-dependent DNA synthesis and enzyme activity-independent glycolysis.

The authors show the dimeric structure of human LYCHOS (lysosomal cholesterol signaling), a fusion of a transporter and a G-protein-coupled receptor-like domain. The study uncovers unique transporter and receptor features and proposes a mechanism to couple cholesterol sensing, transport and signaling.

The authors show that ELL3 maintains chromosomal ploidy by promoting spindle assembly and driving chromosome movement in oocytes. Deficiency of ELL3 results in oocyte aneuploidy and may lead to early miscarriage.

Here the authors show that a gene-inactivating protein complex packs inactive genes into a dynamic and accessible structure. The study challenges the traditional views that restricted accessibility and low dynamics cause gene repression.

A study by Kibe et al. of the translational landscape of HIV-1 reveals alternative translation events, including use of upstream and internal open reading frames, an RNA fold regulating gag-pol frameshifting and ribosome collisions, providing new targets for antivirals.

Using single-molecule microscopy, Jeon et al. study the dynamics of interactions between Spt–Ada–Gcn5 acetyltransferase and transcription activators on both chromatinized and nonchromatinized DNA templates.