Updated resources for exploring experimentally-determined PDB structures and Computed Structure Models at the RCSB Protein Data Bank.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, RCSB.org), the US Worldwide Protein Data Bank (wwPDB, wwPDB.org) data center for the global PDB archive, provides access to the PDB data via its RCSB.

Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes.

In yeast, multiprotein bridging factor 1 (Mbf1) has been proposed to function in the integrated stress response (ISR) as a transcriptional coactivator by mediating a direct interaction between general transcription machinery and the process's key effector, Gcn4. However, mounting evidence has demonstrated that Mbf1 (and its human homolog EDF1) is recruited to collided ribosomes, a known activator of the ISR. In this study, we connect these otherwise seemingly disparate functions of Mbf1.

LARP1 binds ribosomes and TOP mRNAs in repressed complexes.

Terminal oligopyrimidine motif-containing mRNAs (TOPs) encode all ribosomal proteins in mammals and are regulated to tune ribosome synthesis to cell state. Previous studies have implicated LARP1 in 40S- or 80S-ribosome complexes that are thought to repress and stabilize TOPs. However, a molecular understanding of how LARP1 and TOPs interact with these ribosome complexes is lacking.

The RNA helicase HrpA rescues collided ribosomes in .

Although many antibiotics inhibit bacterial ribosomes, loss of known factors that rescue stalled ribosomes does not lead to robust antibiotic sensitivity in , suggesting the existence of additional mechanisms. Here, we show that the RNA helicase HrpA rescues stalled ribosomes in Acting selectively on ribosomes that have collided, HrpA uses ATP hydrolysis to split stalled ribosomes into subunits. Cryo-EM structures reveal how HrpA simultaneously binds to two collided ribosomes, explaining its selectivity, and how its helicase module engages downstream mRNA, such that by exerting a pulling force on the mRNA, it would destabilize the stalled ribosome.

Translation elongation inhibitors stabilize select short-lived transcripts.

Translation elongation inhibitors are commonly used to study different cellular processes. Yet, their specific impact on transcription and mRNA decay has not been thoroughly assessed. Here, we use TimeLapse sequencing to investigate how translational stress impacts mRNA dynamics in human cells.

Genetic screens in Saccharomyces cerevisiae identify a role for 40S ribosome recycling factors Tma20 and Tma22 in nonsense-mediated decay.

The decay of messenger RNA with a premature termination codon by nonsense-mediated decay (NMD) is an important regulatory pathway for eukaryotes and an essential pathway in mammals. NMD is typically triggered by the ribosome terminating at a stop codon that is aberrantly distant from the poly-A tail. Here, we use a fluorescence screen to identify factors involved in NMD in Saccharomyces cerevisiae.

B. subtilis MutS2 splits stalled ribosomes into subunits without mRNA cleavage.

Stalled ribosomes are rescued by pathways that recycle the ribosome and target the nascent polypeptide for degradation. In E. coli, these pathways are triggered by ribosome collisions through the recruitment of SmrB, a nuclease that cleaves the mRNA.

Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome.

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1.

LARP1 senses free ribosomes to coordinate supply and demand of ribosomal proteins.

Terminal oligopyrimidine motif-containing mRNAs (TOPs) encode all ribosomal proteins in mammals and are regulated to tune ribosome synthesis to cell state. Previous studies implicate LARP1 in 40S- or 80S-ribosome complexes that repress and stabilize TOPs. However, a mechanistic understanding of how LARP1 and TOPs interact with these complexes to coordinate TOP outcomes is lacking.

RNF14-dependent atypical ubiquitylation promotes translation-coupled resolution of RNA-protein crosslinks.

Reactive aldehydes are abundant endogenous metabolites that challenge homeostasis by crosslinking cellular macromolecules. Aldehyde-induced DNA damage requires repair to prevent cancer and premature aging, but it is unknown whether cells also possess mechanisms that resolve aldehyde-induced RNA lesions. Here, we establish photoactivatable ribonucleoside-enhanced crosslinking (PAR-CL) as a model system to study RNA crosslinking damage in the absence of confounding DNA damage in human cells.

Bursting translation on single mRNAs in live cells.

Stochasticity has emerged as a mechanism of gene regulation. Much of this so-called "noise" has been attributed to bursting transcription. Although bursting transcription has been studied extensively, the role of stochasticity in translation has not been fully investigated due to the lack of enabling imaging technology.

MutS2 splits stalled ribosomes into subunits without mRNA cleavage.

Stalled ribosomes are rescued by pathways that recycle the ribosome and target the nascent polypeptide for degradation. In , these pathways are triggered by ribosome collisions through recruitment of SmrB, a nuclease that cleaves the mRNA. In , the related protein MutS2 was recently implicated in ribosome rescue.

Dissociating visual perspective taking and belief reasoning using a novel integrated paradigm: A preregistered online study.

There is considerable conceptual overlap between Level-2 Visual Perspective Taking (VPT-2) and Belief Reasoning; both cognitive processes require us to represent another's viewpoint and experience of reality while inhibiting our own egocentric representations. This study investigated if these facets of mentalising are distinct from one another in the general adult population. To do so, we developed a novel "Seeing-Believing Task" with which to compare VPT-2 and true belief (TB) reasoning directly - one in which both judgement types refer to the same state of reality, requiring identical responses, and where self and other perspectives can be dissociated.

The Myxobacterial Antibiotic Myxovalargin: Biosynthesis, Structural Revision, Total Synthesis, and Molecular Characterization of Ribosomal Inhibition.

Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum myxobacterial antibiotic myxovalargin and found it to be extremely potent against . To ensure compound supply for further development, we studied myxovalargin biosynthesis in detail enabling production via fermentation of a native producer.

RCSB Protein Data Bank (RCSB.org): delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), founding member of the Worldwide Protein Data Bank (wwPDB), is the US data center for the open-access PDB archive. As wwPDB-designated Archive Keeper, RCSB PDB is also responsible for PDB data security. Annually, RCSB PDB serves >10 000 depositors of three-dimensional (3D) biostructures working on all permanently inhabited continents.

The Use of Waterless Alcohol-based Antiseptic for Surgical Skin Preparation in Rhesus Macaques ().

Ensuring asepsis of the surgical site before surgery is an essential component of safe surgical practices to reduce the incidence of surgical site infections in veterinary medicine. The current accepted method of skin preparation is a multistep process that alternates either a povidone-iodine or chlorhexidine soap scrub with a 70% alcohol rinse. After cleansing, the site is left to dry before draping.

RCSB Protein Data bank: Tools for visualizing and understanding biological macromolecules in 3D.

Now in its 52nd year of continuous operations, the Protein Data Bank (PDB) is the premiere open-access global archive housing three-dimensional (3D) biomolecular structure data. It is jointly managed by the Worldwide Protein Data Bank (wwPDB) partnership. The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) is funded by the National Science Foundation, National Institutes of Health, and US Department of Energy and serves as the US data center for the wwPDB.

Distinct elongation stalls during translation are linked with distinct pathways for mRNA degradation.

Key protein adapters couple translation to mRNA decay on specific classes of problematic mRNAs in eukaryotes. Slow decoding on non-optimal codons leads to codon-optimality-mediated decay (COMD) and prolonged arrest at stall sites leads to no-go decay (NGD). The identities of the decay factors underlying these processes and the mechanisms by which they respond to translational distress remain open areas of investigation.

Physical activity and perceived barriers in individuals with moderate-to-severe traumatic brain injury.

Introduction: Regular physical activity (PA), especially aerobic exercise, may benefit cognitive function in middle-aged and older adults, but promoting regular PA in individuals with traumatic brain injury (TBI) remains a challenge.

Objective: To characterize PA and perceived barriers to PA in younger (<45 years) and middle age and older (≥45 years) individuals ≥1 year after moderate-to-severe TBI.

Design: Multicenter survey study.

Ribosome collisions induce mRNA cleavage and ribosome rescue in bacteria.

Ribosome rescue pathways recycle stalled ribosomes and target problematic mRNAs and aborted proteins for degradation. In bacteria, it remains unclear how rescue pathways distinguish ribosomes stalled in the middle of a transcript from actively translating ribosomes. Here, using a genetic screen in Escherichia coli, we discovered a new rescue factor that has endonuclease activity.

Evolutionarily conserved inhibitory uORFs sensitize mRNA translation to start codon selection stringency.

Translation start site selection in eukaryotes is influenced by context nucleotides flanking the AUG codon and by levels of the eukaryotic translation initiation factors eIF1 and eIF5. In a search of mammalian genes, we identified five homeobox () gene paralogs initiated by AUG codons in conserved suboptimal context as well as 13 genes that contain evolutionarily conserved upstream open reading frames (uORFs) that initiate at AUG codons in poor sequence context. An analysis of published cap analysis of gene expression sequencing (CAGE-seq) data and generated CAGE-seq data for messenger RNAs (mRNAs) from mouse somites revealed that the 5' leaders of mRNAs of interest contain conserved uORFs, are generally much shorter than reported, and lack previously proposed internal ribosome entry site elements.