Articles

Shajahan et al. unveil a repressive genomic compartment in totipotent-like cells, shaped by Zscan4 and guided by transient Z-DNA formation. This ‘Z compartment’ may be crucial for preserving totipotency in early embryos.

Tafur et al. determined the cryo-electron microscopy structure of the SEA complex (GATOR) bound to its substrate, the EGO complex (Ragulator–Rag), and showed that its GAP activity is essential for both rapid inactivation and reactivation of TORC1.

Fang et al. reveal how a bacterial circadian clock turns genes on and off at the right times of day and use the purified proteins to drive circadian gene transcription in a test tube for days.

Scholl et al. show that PopZ forms filamentous condensates driven by its helical domain and inhibited by its disordered region. Phase-dependent conformations modulate client interactions and disruption of filamentation or condensation impairs cellular function and growth.

Nagahata, Kato and Yamada et al. provide cryo-electron microscopy structures of four phylogenetically diverse RNA-guided nucleases—HfmIscB, TbaIscB, YnpsCas9 and NbaCas9—each in complex with its guide RNA and target DNA, providing insights into CRISPR–Cas9 evolution.

Annunziato, Quan and Donckele et al. identify G3BP2 (Ras–GAP SH3 domain-binding protein 2) as a molecular glue-induced neosubstrate of the CRL4^CRBN E3 ubiquitin ligase. The CRBN–glue neosurface uses a molecular surface mimicry mechanism to recruit and degrade G3BP2 in a compound-dependent manner.

Yu, Yin, Zhu, Lu and colleagues show that Acr inhibits Cas activity through a scaffold RNA interaction and further develop an RNA truncation optimization strategy to enhance editing performance.

Kim, Wang, Clow and colleagues show that long-range chromatin loops bringing distal enhancers or super-enhancers together with promoters are cohesin dependent and cell type specific, whereas most short-range and promoter-centric transcriptional loops are cohesin independent and constitutive.

Chen et al. show that redox signals activate ADAR1 to fix faulty RNA pieces during DNA copying, ensuring smooth replication and protecting genome stability.

Ahmad et al. show that soluble histone H4 binds at histone genes and acts as a repressor of their expression. These findings suggest that histone H4 is a sensor of ongoing DNA replication. Ongoing chromatin assembly uses up soluble H4 and relieves histone gene repression; however, once DNA replication ceases, soluble H4 accumulates and represses the histone genes.

Here, the authors generated and analyzed run-on sequencing data to observe transcription in species across the tree of life to uncover the origins of the promoter-proximal pause.

Zeng et al. applied single-particle cryo-electron microscopy to native samples isolated from the human parasite Toxoplasma gondii, determining multiple structures of key components of the conoid, a cone-shaped organelle essential for host cell invasion.

Riechmann et al. uncover structural features governing ubiquitin transfer from ubiquitin-activating E1 enzymes UBA1 and UBA6 to specific E2 ubiquitin-conjugating enzymes, revealing a hierarchy of E2 activity with cognate E1s.

Mitochondrial translational activators (TAs) facilitate transcript-specific translation. Using selective ribosome profiling and cryo-electron microscopy, the authors show that TAs bind to the 5′ untranslated region of their target transcript to position mitoribosomes for initiation.

Vidmar et al. use cryo-EM to reveal how bacterial RNA polymerase (RNAP) and topoisomerase I (TopoI) cooperate. TopoI switches conformation, senses DNA supercoils near RNAP and relaxes them. Mutations disrupting this process alter bacterial motility and operon polarity.

By reconstituting and visualizing mammalian transcription elongation at the single-molecule level, Wang et al. dissected the effects of individual elongation factors on the speed of RNA polymerase II, which is found to operate as a multi-gear molecular machine.

Carty et al. identify the H3K9 methyltransferases that restrict the size and position of the centromere protein A chromatin domain, maintaining functional centromeres.

Mi et al. use de novo protein design to address bystander and off-target editing in base editing, resulting in a highly precise mitochondrial cytosine base editor that is valuable for studying and treating mitochondrial diseases.

Elhan et al. show that ATG2A acts with DGAT2, the enzyme producing triacylglycerol (TAG), in lipid droplet growth. By delivering diacylglycerol to lipid droplets, ATG2A not only fuels TAG production but also promotes the recruitment of DGAT2 to droplet surfaces.

Baretić and Missoury et al. identify vertebrate proteins FAM118B and FAM118A as sirtuins similar to bacterial antiphage enzymes and show that FAM118A/B processing of NAD involves head-to-tail filament formation and a partnership between the two paralogs.