Research articles

Examining artificial embryos (gastruloids), Merle et al. uncover precise gene organization and proportional growth, providing insights into fundamental principles of developmental processes in mammalian systems.

The DNA polymerase α–primase complex undergoes dramatic configurational rearrangements to synthesize chimeric RNA-DNA primers across two separate active sites while maintaining simultaneous interactions at opposite ends of the primer–template duplex.

The biogenesis and recycling of the ‘heart’ of the human spliceosome, the U5 small nuclear ribonucleoprotein (snRNP), requires CD2BP2 and TSSC4. Here the authors present cryo-electron microscopy structures that reveal how these protein chaperones orchestrate the ATP-independent (re)generation of the U5 snRNP.

Here the authors report the structure of the human 20S U5 snRNP, providing new insights into the assembly of the spliceosome building blocks.

Here, the authors determine the structure of the human outer kinetochore KMN network complex, showing that it forms an extended and rigid rod-like structure and that it exists in an auto-inhibited state which can be relieved by phosphorylation.

During cell division, kinetochores anchor chromosomes to spindle microtubules. Here, the authors report a comprehensive structure–function analysis of the kinetochore’s main microtubule receptor, the KMN network, shedding new light on its organization.

Here, the authors report the structure of the native Commander complex and reveal key interactors by mass spectrometry-based proteomics.

Here, the authors ask how much regulatory activity DNA is expected to have in the absence of selection. In yeast and humans, they find that gene regulatory activity is common in evolutionarily naive DNA, suggesting that activity is not always indicative of function.

JADE is a subunit of human acetyltransferase complex HBO1 that is essential in transcriptional regulation. Gaurav et al. characterize the molecular mechanism by which JADE mediates genomic association and enzymatic and pathological activities of the HBO1 complex.

A calcium ion binding site, hidden in the highly conserved gate of the synaptic AMPA-type ionotropic glutamate receptor, reveals upon gating and controls ion transport across the membrane, providing new mechanistic insights on ion permeation.

The authors determined a cryo-EM structure of the pioneer factor NR5A2 bound to a nucleosome. NR5A2 releases nucleosomal DNA from histones by DNA minor anchor groove competition, providing a mechanism for pioneer factor activity during reprogramming

Using biochemistry, cell biological, X-ray crystallography and cryo-EM methods, Maisonneuve et al. reveal how the scaffolding proteins CNK and HYP enhance the binding of KSR to MEK, which in turn allosterically controls RAF activation in Drosophila.

Researchers unveiled the structural details of sphingomyelin synthase (SMSr), shedding light on its role in sphingolipid biosynthesis. SMSr transfers the phosphoethanolamine from PE to ceramide, adding complexity to the field of lipid homeostasis.

Here, using mathematical modeling and an in vitro deadenylation system, the authors quantitatively demonstrate the effect of non-adenosines in the poly(A) tail and exemplify how tail sequence regulates mRNA stability.

By investigating key transcription factors in Drosophila, the authors show that pioneering activity is not an intrinsic, binary property. Instead, it is heavily influenced by the level of chromatin occupancy of the transcription factors, which is controlled by multiple protein domains and protein-extrinsic features.

Isaac et al. present mtFiber-seq, a method that measures individual mitochondrial genome packaging at nucleotide resolution. They show that most nucleoids are in an inaccessible state, modulated by the abundance of the DNA-binding protein TFAM.

Using deep mutational scanning, the authors uncover the functional consequence of missense mutations in ARID1B, a subunit of the SWI/SNF chromatin remodeling complex that is frequently mutated in human Coffin–Siris syndrome and in cancer.

Kalienkova et al. use cryo-electron microscopy to capture 3D structures of a neuropeptide-gated DEG/ENaC ion channel in resting and ligand-bound states, detailing the mechanism by which peptides activate these excitatory ion channels.

Here, upon obtaining cryo-EM structures of CRL3^KBTBD2 in seven states, the authors propose a model for the activation cycle of CRL3 ligases, including assembly, substrate recruitment, (de)neddylation and CAND1-mediated substrate receptor exchange.

Using cryo-EM, authors reveal the structure and activation mechanism of GPR156, a class C orphan GPCR implicated in sound detection. They find that GPR156 is a transducer for phospholipid signaling and provide insights into the basis for its constitutive activation.