Articles

Here, Isaacs, Nieto and Zhang et al. discover a potent nanobody and engineer a dual-action antibody that targets two viral proteins, offering strong protection against Nipah and Hendra viruses while preventing viral escape, potentially contributing to future treatments.

Florez Ariza and Lue et al. use cryo-electron microscopy to investigate how the RECQL5 helicase regulates transcription. Their structural findings suggest that RECQL5 can modulate RNA polymerase II’s translocation state, potentially restarting stalled transcription.

Using cryo-electron microscopy and biochemistry, Zhang et al. reveal that the DNA helicase RECQL5 and the transcription-coupled DNA repair complex coordinate to regulate transcription elongation rates and maintain genome stability.

Dubiez and colleagues present a cryo-EM structure of the complex responsible for nuclear export of pre-small nuclear RNAs, comprising CBC–PHAX–CRM1–RanGTP. The structure provides insights into the complex architecture, assembly and target RNA recognition.

Khan et al. show that Sec18 uses both D1 and D2 AAA+ rings cooperatively, opening them laterally for SNARE substrate loading and for subsequent release of SNAREs.

Licensing of eukaryotic origins of replication with MCM double hexamers (DHs) can occur through distinct pathways. Here, Lim et al. show that in yeast, cell cycle-dependent regulation of DH formation by CDK and origin structure have co-evolved.

Carmona-Rosas, Li and Smith et al. show that two cell surface receptors, latrophilin and Toll-like receptor, interact in Caenorhabditis elegans and mediate strong roles in early development and morphogenesis.

Zhao et al. uncover the protein composition and atomic structure of ciliary radial spoke 3, revealing it as a metabolic hub that regulates ciliary motility, providing insights into ciliary diseases

Köhler et al. present the crystal structure of fungal tRNA ligase Trl1-LIG bound to an activated RNA substrate, providing key insights into conserved substrate binding and activation, enzyme specificity and a tRNA substrate coordination model.

Xia et al. show how p53, guided by cis-regulatory sequences and cofactors (purine-rich element binding protein B and HOX transcript antisense RNA), orchestrates promoter-specific transcriptional regulation.

Miao et al. show that loss of neuronal Vps13d in mice leads to mitochondrial dysfunction, GSDME-mediated mitochondrial DNA release, cGAS–STING inflammatory signaling and activation of microglia, culminating in neuronal loss.

Wu et al. shed light on the role of peroxisomal biogenesis factor 14 (PEX14) in peroxisomal protein import. They show that PEX14 condensates recruit the receptor PEX5 loaded with peroxisome-targeting signal 1 (PTS1) clients or PTS2 clients bound to receptor PEX7.

Zeinert et al. provide cryo-EM structures of the E. coli Mg²⁺ importer MgtA: unexpectedly, this P-type ATPase is a dimer with an uncommon transmembrane ion-binding site and knotted N-terminus, which are functionally important features.

Rashan, Bartlett and colleagues show that mammalian 4-hydroxy fatty acids are primarily catabolized by ACAD10 and ACAD11 (atypical mitochondrial and peroxisomal acyl-CoA dehydrogenases, respectively) that use phosphorylation in their reaction mechanisms.

The authors reveal that, in fruit fly ovaries, the protein Rhino is guided to specific regions of the genome by a combination of two histone modifications, enhancing understanding of how cells protect their DNA from harmful virus-like elements.

Lee et al. show that DMXL1, a regulator of V-ATPase assembly, is recruited to lysosomes upon TRPML1 activation in a manner dependent on conjugation of ATG8 proteins on lysosomal membranes (CASM) and promotes lysosomal function.

Multiplexed assays of variant effect can resolve clinical variants but are incompatible with secreted proteins. Here Popp et al. develop MultiSTEP, a generalizable surface-tethering method to assess variant effects in secreted proteins at scale.

Mei et al. profile H2A variant distribution in mouse oocytes, revealing broad H2A.Z domains at intergenic regions in which H2A.Z and MLL2-mediated H3K4me3 reinforce each other. H2A.Z is vital for oocyte development.

Xu et al. establish the importance of H2A.Z in mouse oocyte development. H2A.Z is incorporated into chromatin at promoters and putative enhancers, and its presence promotes histone acetylation in fully grown oocytes.

Here, Rangan et al. characterize S. cerevisiae intron structures with in vivo transcriptome-wide structure probing, showing that certain introns exhibit structural features that distinguish pre-mRNA from spliced mRNA and contain structures that regulate gene expression.