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Replication-dependent histone mRNA decay involves the RNA helicase UPF1, the histone stem-loop binding protein SLBP and the exoribonuclease 3’hExo. Here, the authors present evidence for assembly of a degradosome-like complex involving the three proteins and delineate the mechanism that drives their concerted action to achieve histone mRNA decay.

Auvray and colleagues present a covalent fluorescent probe targeting tubulin, a key cytoskeletal protein. The probe is cell-permeable, fluorogenic, and STED-compatible, enabling clear, minimally-invasive imaging of dynamic processes in live and fixed cells.

Mutations in elongation factor G protect bacteria from aminoglycoside antibiotics through unknown mechanisms. Here, the authors show that the mutations selectively slow the movement of antibiotic-bound ribosomes along mRNA, which prevents error-prone protein synthesis and thus membrane damage and antibiotic uptake.

Splicing is carried out within a large structure, the spliceosome, containing many RNAs and proteins. In this paper, two intermediary complexes of the splicing reaction have been purified. The differences in these complexes provide a significant advancement in understanding of the composition of the catalytic core.

H3K36me3 is a marker of actively and recently transcribed genes. Here, the authors describe a 3-step mechanism of transcription-coupled H3K36me3 deposition by the mammalian methyltransferase SETD2, via the elongation factor SPT6.

Ubiquitination is a versatile modification system in eukaryotic cells. Here, the authors unveil that the ubiquitin ligase HUWE1 can modify drug-like small-molecule substrates, beyond proteins. This discovery may be harnessed to develop specific tool substrates or inhibitors of HECT-type ligases.

Harasimov, Gorry, Welp, Penir, Horokhovskyi et al. analyse proteostasis in mammalian oocytes and ovaries: the maintenance of oocytes involves exceptional protein longevity, and many of the extremely long-lived proteins decline as the ovary ages.

Although IWS1 has been implicated in transcription-coupled processes, its direct role in RNA polymerase II function remained undefined. Here, the authors demonstrate that IWS1 enhances Pol II elongation velocity by acting as a structural scaffold and promoting co-transcriptional H3K36me3 deposition.

RNA interaction sites on proteins are detected using UV-based cross-linking, mass spectrometry analysis and a dedicated data analysis workflow.

Lavdovskaia, Hanitsch, Linden et al. provide a comprehensive roadmap of mitoribosome biogenesis and establish that mitochondria use a unique pathway for the assembly of their translation machinery.

Bicarbonate (HCO₃⁻) is critical in sperm for stimulation of cAMP synthesis during fertilization, though there is dispute over how  HCO₃⁻ is transported into sperm. Here the authors use limit-of-detection LC/MS to characterize sperm protein expression and show that HCO₃⁻ is produced from CO₂ diffusion into sperm rather than active transport.

Sala et al. report the first structural snapshot of the Nipah virus RNA-dependent RNA polymerase in the actively elongating state, uncovering key mechanisms of RNA synthesis by non-segmented negative strand RNA viruses.

Cross-linking mass spectrometry (XLMS) allows mapping of protein-protein and protein-RNA interactions, but the analysis of protein-DNA complexes remains challenging. Here, the authors develop a UV light-based XLMS workflow to determine protein-DNA interfaces in reconstituted chromatin and isolated nuclei.

Comprehensive quantitative profiling of intact glycopeptides remains technically challenging. To address this, the authors here develop an integrated quantitative glycoproteomic workflow, including optimized sample preparation, multiplexed quantification and a dedicated data processing tool.

Aminoglycoside antibiotics target the ribosome and induce misreading, yet which translation errors induce bacterial cell death is unclear. Here authors use quantitative mass spectrometry and show that bactericidal aminoglycosides induce clusters of errors in full-length proteins in vivo with as many as four amino acid substitutions in a row.

The Paf1 complex (Paf1C) is an elongation factor assembly that forms the interface between transcribing Pol II and chromatin factors. Here the authors describe the architecture of Paf1C and its interface with Pol II, and show that Paf1C is globally required for normal mRNA transcription in yeast.

Here, the authors provide insights into a splicing quality control mechanism. The Gpl1–Gih35 complex binds to the active site of aberrant spliceosomes, blocks splicing progression and triggers the spliceosome discard pathway.

PRPF8 is a hotspot for mutations causing retinitis pigmentosa-type 13. Here the authors generated PRPF8 patient-specific retinal cells, demonstrating an important role for this splicing factor in spliceosome kinetics and 5’ splice site selection.

Regulation of thymocyte development by RNA-binding proteins is not fully characterized. Here the authors show the RBP ARPP21 interacting with the Rag1 3’-UTR to promote Rag1 expression, TCR rearrangement and an increased diversity of the TCR repertoire and that ARPP21 is down regulated by TCR stimulation.

Using cryo-EM, SAXS and HDX–MS, the authors mechanistically delineate dimerization-induced autoinhibition of the HECT-type ligase HACE1 and the selectivity of the active ligase monomer for GTP-bound RAC1.

Measuring precise protein turnover rates in animals is technically challenging at the proteomic level. Here, Fornasiero and colleagues use isotopic labeling with mass spectrometry and mathematical modeling to accurately determine protein lifetimes in the mouse brain

While archaeal proteomics advanced rapidly, a comprehensive proteome database for archaea is lacking. Therefore, the authors here launch the Archaeal Proteome Project, a community-effort providing insights into archaeal cell biology via the combined reanalysis of Haloferax volcanii proteomics data.

Dysfunctions of the mitochondrial OXPHOS system lead to severe human disorders. Here, the authors analyzed a mouse mutant that mimics a mitochondrial disorder patient and find that reactive oxygen species trigger RNA release and inflammatory pathway in liver.

Cryo-EM elucidation of a fully reconstituted Pol II–DSF–PAF1–SPT6 elongation complex defines the position of PAF1 subunit RTF1 and reveals contacts with the Pol II bridge helix that may allosterically stimulate transcription elongation.

Cryo-electron microscopy structures of cross-exon pre-B and B-like complexes contribute new insights into the molecular mechanisms that mediate the switch from a cross-exon to a cross-intron organized spliceosome.

Alzheimer’s disease is characterized by the accumulation of aggregated tau protein. Here the authors find that Hsp chaperones, which normally protect cell homeostasis, can assemble with co-chaperones in a “multichaperone machinery” to target tau aggregation.

Cryo-EM structures of the transcription preinitiation complex in the presence of the +1 nucleosome show how the general transcription factor TFIIH can interact with the nucleosome at several positions.

Do proteasomes catalyze peptide splicing? Here, the authors develop and apply a method to identify spliced peptides produced from entire proteins, confirm that proteasomes produce a sizeable variety of cis-spliced peptides with well-defined characteristics, and show that non-spliced and spliced peptides are concentrated in hotspots.

Here the authors visualize the workings of ELOF1 in transcription-coupled DNA repair, showing that ELOF1 repositions repair factors on the surface of DNA damage-stalled RNA polymerase II to facilitate its ubiquitylation by the CRL4^CSA E3 ligase and inactivation by UVSSA.

Cryo-electron microscopy structures of the human Integrator complex in three different functional states shed light on how Integrator terminates RNA polymerase II (Pol II) transcription by disengaging Pol II from the DNA template.

The authors resolve the structure of five complexes containing RNA polymerase II and the CSA and CSB proteins, offering insight into how the repair of DNA lesions is coupled to transcription.

The cryo-electron microscopy structure of a newly identified, early spliceosomal complex reveals the mechanism by which the RNA helicase Prp5 enhances the fidelity of the excision of introns from precursor mRNAs.

A NOS bridge between cysteine and lysine residues serves as an allosteric redox switch in the transaldolase enzyme of Neisseria gonorrhoeae, demonstrating the existence of protein regulatory switches that contain covalent crosslinks other than disulfides.

Maturation of the ribosomal peptidyl transferase center (PTC) is mediated by universally conserved GTPases. Here, cryo-EM structures of mitochondrial ribosomal large subunit assembly intermediates and of mature ribosomes offer insight into the roles of several assembly factors, including GTPBP6’s role in both ribosome biogenesis and recycling.

Using cryo-EM, here the authors structurally delineate the Elongin–RNA polymerase II holocomplex. They show that Elongin allosterically regulates the transcribing RNA polymerase II via a latch that affects its conformational mobility.

The characterization of the type IV CRISPR system from Aromatoleum aromaticum shows that Csf2 serves as a backbone to which Csf5, Csf3 and Csf1 bind to form CRISPR–ribonucleoprotein complexes. Csf5 (a Cas6 variant) generates CRISPR RNAs with short, 7 nucleotide 5′-repeat tags and stable 3′ hairpin structures.

The NER machinery contains the multisubunit transcription factor IIH (TFIIH) that opens the DNA repair bubble, scans for the lesion, and coordinates excision of the damaged site. Here the authors resolve the cryo-electron microscopy structure of the human core TFIIH-XPA-DNA complex and provide insights into its activation.

The cryo-EM structure of human U2 small nuclear ribonucleoprotein (snRNP) offers insights into what rearrangements are required for this snRNP to be stably incorporated into the spliceosome, and the role that the DEAD-box ATPase PRP5 may have in these rearrangements.

The cryo-electron microscopy structure of a paused transcription elongation complex of RNA polymerase II bound to DRB sensitivity-inducing factor and negative elongation factor is reported at 3.2 Å resolution.

The cryo-electron microscopy structure of the 16-subunit yeast SWI/SNF complex RSC in complex with a nucleosome substrate provides insights into the chromatin-remodelling function of this family of protein complexes.

The Staufen proteins recognize secondary structures in 3’-untranslated regions in mRNA transcripts and induce degradation of these mRNAs with the help of the RNA helicase UPF1. Here the authors report that the nonsense-mediated mRNA decay factor UPF2 mediates the interaction between Stau1 and UPF1 in Staufen-mediated mRNA decay.

Structural studies on the yeast transcription coactivator complex SAGA (Spt–Ada–Gcn5–acetyltransferase) provide insights into the mechanism of initiation of regulated transcription by this multiprotein complex, which is conserved among eukaryotes.

Cryogenic electron microscopy images of a spliceosome complex undergoing catalytic activation provide mechanistic insight into how the two ATP-dependent RNA helicases involved in this process, PRP2 and Aquarius, work together.

Bacteriophage T4 uses an enzyme known as ADP-ribosyltransferase ModB to modify the translational apparatus of bacteria it infects, not only by ADP-ribosylating proteins, but also by attaching entire RNA chains in a process known as RNAylation.

ASCC3 is a multi-functional helicase that contains two consecutive Ski2-like helicase units. Here, the authors show that ASCC3 can unwind DNA by threading one strand of a substrate duplex through both helicase units, supported by the TRIP4 protein.

The ribosomal stalk L12 is the only multi-copy protein in the ribosome and is essential for translation. Here Davydov et al.use a bioinformatics and mass spectrometry approach to study the evolution of L12 in bacterial ribosomes and predict its stoichiometry in a wide range of species.

Heterochromatin protein 1 (HP1), including HP1 α, β and γ, is a family of non-histone chromatin factors thought to be involved in chromatin organization. Here, the authors show that dimeric HP1β interacts dynamically with H3K9me3, a hallmark of heterochromatin, and bridges condensed chromatin.