Browse Articles

In this Perspective, the authors propose a framework to explain membrane protein biogenesis, wherein different parts of a nascent substrate are triaged between Oxa1 and SecY family members for insertion.

Oncoprotein transcription factor MYC undergoes phase separation, forming transcriptionally active condensates. The chemogenetic tool SPARK-ON reveals that MYC phase separation selectively modulates the transcriptome and promotes cell proliferation.

Here, using cryo-EM and biochemistry, the authors delineate how the XPD helicase unorthodoxly uses its Arch domain to separate double-stranded DNA upon approaching a DNA lesion, promoting our understanding of NER bubble formation and damage verification.

The molecular mechanisms that regulate the transition from totipotency into divergent cellular states are unclear. Two new studies show that the transcription factors TFAP2C, NR5A2 and TEAD4 (TNT) support the formation of a transient bipotent state by activating early pluripotency and trophectoderm genes and modulating HIPPO signaling.

Here the authors identify the transcription factors TFAP2C and TEAD4 as a bistable switch that reconciles into Hippo ON and OFF states, establishing a composite state at the eight-cell stage and critically regulating lineage diversification.

The authors solve a cryo-EM structure of the regulatory subunit of human protein phosphatase 2A in complex with HIV-1 Vif-containing E3 ligase, leading to improvement of our understanding of host–virus protein interactions.

The commander complex was recently shown through interactomic screens to be a ubiquitous and conserved protein complex with fundamental biological roles. Two recent reports together revealed the structure of the complete commander assembly and explored its functional implications.

Here the authors show that active DNA demethylation and transcription factor occupation at distal regulatory elements is essential for pluripotency maintenance in dormancy conditions.

Using time-resolved cryo-EM, the authors capture complete structural snapshots of the enzymatic cycle coupled with channel gating in a TRPM-type channel enzyme.

The authors revealed that the general translation factor eIF4A exerts a repressive effect on a subset of mRNAs by enhancing LARP1 and TOP mRNAs during mTORC1 inhibition under stress.

This issue of Nature Structural & Molecular Biology presents studies investigating RNA processing, including mechanisms of splicing, biogenesis of the splicing machinery, decoding of mRNA by the ribosome, and deadenylation of mRNA for degradation. We are also delighted to be publishing News & Views and Comment pieces that reflect on these exciting advances in the field.

NAD(H) redox homeostasis has a fundamental role in cellular metabolism. We screened for potential modulators of NAD(H) using a genome-scale RNA interference (RNAi) approach combined with SoNar, a high-performance sensor that is sensitive to the redox state of NAD(H). Our analysis identified HES4 as a negative regulator of the NADH/NAD⁺ ratio that influences pyrimidine biosynthesis and exerts a potent oncogenic effect.

Hexasomes are non-canonical nucleosomes that package DNA with six instead of eight histones. Here, the author contextualizes two recent studies on the interplay of the chromatin remodeler INO80 with hexasomes with historical literature on the subject.

This study reports the structure of lysosomal N-acetyltransferase HGSNAT providing insights into the mechanism of lysosomal transmembrane acetylation of heparan sulfate required for its catabolism.

The authors identify genes potentially involved in NAD(H) redox modulation and provide insight on major hit HES4, which uses its transcriptional repressive function to drive pyrimidine nucleotide biosynthesis and tumor growth.

Here the authors used cryogenic electron microscopy and biochemistry to understand how yeast Mcm10 exerts its essential role in DNA replication initiation, finding that it splits the double Cdc45-MCM-GINS-Polε structure. The lagging-strand template is ejected from each MCM ring as the central channel of the helicase becomes too tight to accommodate two DNA strands.

Here, using cryo-EM, the authors reveal the mechanism by which RecA filamented on single-stranded DNA binds to and induces LexA cleavage, the key signal governing the bacterial DNA damage response pathway implicated in antibiotic resistance.

Since Nature Structural and Molecular Biology was started 30 years ago, our understanding of transcription and mRNA processing has been revolutionized through structural and mechanistic studies. Here, we present our personal views of the advances in understanding the production of mature eukaryotic mRNAs over the past decade.

Branch point selection is required for pre-mRNA splicing, and its mis-regulation is associated with many diseases. Two structural studies provide insights into the dynamics of active site formation and the spliceosomal proteins that may contribute to activation of the correct branch point in eukaryotic introns.

Targeted biologics delivery requires programming multicomponent protein nanomaterials to enable selective targeting and response to environment changes in a single unified framework. A novel protein nanoparticle platform has been designed to modulate cell-surface target specificity, cargo packaging, and pH-dependent release of encapsulated cargo, providing exciting possibilities in biologics delivery.