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In this Review, Kotani and Nakatogawa discuss recent advances in our understanding of the molecular basis of autophagy induction and delineate how diverse mechanisms converge on core principles to ensure context-specific control of autophagy initiation.
Huang, Rigau and colleagues observe major changes in how DNA is organized in early germ cells before they start developing into sperm or eggs. These results show that germline removes structural ‘memory’ of DNA folding to start fresh for the next generation.
In this issue of Nature Structural & Molecular Biology, we are publishing two studies investigating the mechanisms of how bacteria fight phage invasion, and how phages fight back.
This study shows how the bacterial retron Eco2 defends against viruses. Phage nucleases trigger activation of Eco2, which cuts RNAs, shuts down protein production and stops phage replication.
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.
Pindi and Palermo review the contributions of deep learning structure prediction algorithms, physics-based simulations, neural networks, graph neural networks and generative models in engineering CRISPR systems and in understanding their mechanistic basis.
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.
Transcription is tightly regulated and universal across all domains of life. A study proposes how, during eukaryotic evolution, the emergence of a regulatory mechanism consisting of a focused promoter-proximal pause of RNA polymerase II could have originated from a proto-pause with the acquisition of negative elongation factor (NELF) subunits.
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.
Accurately interpreting density maps into atomic models is a central yet challenging goal of cryo-EM. Two studies now reveal distinct ways in which protein structure prediction can be incorporated into cryo-EM model building to enable more accurate and robust automated construction of protein atomic models from density maps.
For Okazaki fragments to efficiently mature, RNA primers need to be removed. A recent study in Nature Structural & Molecular Biology implicates ADAR1 in editing mismatched primers to promote unabated lagging-strand synthesis, via oxidation-dependent dimerization and activation of ADAR1.
Annunziato, Quan and Donckele et al. identify G3BP2 (Ras–GAP SH3 domain-binding protein 2) as a molecular glue-induced neosubstrate of the CRL4CRBN 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.