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Herpes simplex virus 1 (HSV-1) infection disrupts transcription termination by RNA Polymerase II. Here, Djakovic et al. identify the immediate-early protein ICP22 protein of HSV-1 to induce open chromatin downstream of genes upon read-through transcription involving the histone chaperone FACT.

Heim et al. investigate the role of CD8⁺ T cells specific to HBV polymerase in the context of chronic HBV infection. They identify a unique subset of CD8⁺ T cells with an attenuated effector function. The attenuation is driven by TGFβ signaling, offering new insights into the immune landscape of chronic HBV infection and suggesting potential therapeutic avenues for modulating these cells to enhance viral control.

RNA polymerase (Pol) I transcribes the ribosomal RNA precursor in eukaryotes. Here, the authors present three cryo-EM structure of S. pombe Pol I in different functional states among them a dimer structure and discuss conserved and organism-specific features of Pol I.

Here they show that SSUP-72/PINN-1 regulates Pol II 3′ pausing and transcription termination in C. elegans. Its loss bypasses the need for CDK-12 during development, uncovering a novel mechanism that coordinates operonic gene expression and ensures proper growth.

A study by Kibe et al. of the translational landscape of HIV-1 reveals alternative translation events, including use of upstream and internal open reading frames, an RNA fold regulating gag-pol frameshifting and ribosome collisions, providing new targets for antivirals.

RNA polymerase II (Pol II) uses a DNA template to direct RNA synthesis during transcription, but there is also emerging evidence that it can use RNA as a template. In this paper the RNA-dependent RNA polymerase activity of Pol II is biochemically and structurally characterized.

The crystal structure of the yeast RNA Pol II elongation complex bound to the inhibitor α-amanitin is solved, revealing that two functional elements, the trigger loop and the bridge helix, are trapped in a position different from their pre- and post-translocation states. This is proposed to be a translocation intermediate, lending support to a Brownian ratchet mechanism for RNA Pol II translocation during elongation.

An anti-HIV-1 antibody that targets an N332_gp120 glycan-independent V3 epitope, a site of Env vulnerability, can decline viremia in HIV-1-infected humanized mice while overcoming classical V3 escape mutations.

In the layered magnetic semiconductor CrSBr, emergent light–matter hybrids (polaritons) increase the spectral bandwidth of correlations between the magnetic, electronic and optical properties, enabling largely tunable optical responses to applied magnetic fields and magnons.

Membrane receptor kinases are involved in many signalling pathways in plants. Here, the authors show that a common mechanism, consisting of a RLCK kinase and a PP2C phosphatase, regulates signalling downstream of receptors, both in immunity and development.

HIV remission of more than 6 years was achieved in a patient with functional viral co-receptors after CCR5 wild-type/Δ32 allogeneic stem cell transplantation, providing evidence of other mechanisms that can be harnessed to attain long-term remission.

The combination of single-molecule fluorescence resonance energy transfer measurements of multiple dye pairs with probabilistic data analysis allows quantitative measurement of the position of flexible domains in macro-molecular complexes. The method was used to determine the three-dimensional probability density of the position of RNA exiting the transcription elongation complex.

XPD is part of the TFIIH complex which plays major roles in transcription initiation and nucleotide excision repair (NER). Here the authors present a high-resolution crystal structure of the XPD-MAT1 interface and dissect the role of this interface in transcription and NER.

The MYST acetyltransferase HBO1 is a critical regulator in maintaining leukaemia stem cells, and a small-molecule inhibitor of HBO1 is developed that shows efficacy against a range of acute myeloid leukaemia cells.

Klein and colleagues characterize 04_A06, a new V_H1-2-encoded broadly neutralizing antibody that has marked breadth and potency against extended multiclade HIV-1 pseudovirus panels and can maintain full viral suppression in HIV-1-infected humanized mice.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

This is the first report on a virus infecting the amoeboflagellate Naegleria, including the lethal human pathogen N. fowleri. The new virus isolate, Catovirus naegleriensis (Naegleriavirus, NiV), shows hallmarks of giant viruses (Nucleocytoviricota) and unique adaptations to its protist host.

Dirk Schübeler and colleagues report an experimental strategy to identify genetic elements that autonomously determine DNA methylation states in murine stem cells. They identified promoter sequences that supported proper de novo methylation during differentiation and determined that this activity is contained within small methylation-determining regions.

Release of inorganic phosphate (P_i) from actin marks older actin filaments for disassembly. Here, the authors show how P_i exits the F-actin interior through a ‘molecular backdoor’. The backdoor arrangement is distorted in a disease-linked actin variant.

Targeting a non-natural micropeptide ‘killswitch’ to several biomolecular condensates altered condensate compositions and revealed condensate functions in human cells

A method to label and visualize nascent RNA allows real-time study of transcriptional dynamics at single-cell resolution in vivo. The approach is used to study transcriptional repression of the SPX1 gene by phosphate in Arabidopsis roots.

HIV-1 viral gene expression stochastically switches between active and inactive states. Here, using improved single molecule RNA microscopy, the authors show that HIV-1 RNA stochastic transcription is achieved by groups of closely spaced polymerases, and is regulated by Mediator and TBP at different time scales.

Neutralization of the SARS-CoV-2 Omicron variant is markedly impaired in sera from recipients of two doses of the COVID-19 vaccine BNT162b2 or from convalescent individuals, but is robustly increased in both groups following a booster vaccine dose.

Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.

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.

Genes encoding protein complex subunits are often dispersed in the genome of eukaryotes, raising the question how these protein complexes assemble. Here, the authors provide evidence that mammalian nuclear transcription complexes are formed co-translationally to ensure specific and functional interactions.

Different mechanisms have been reported to explain resistance to chemotherapy in cancer. Here, the authors show that the chemotherapeutic drug 5-fluorouracil alters the function of ribosomes to promote pro-survival gene translation leading to chemotherapy resistance.

BCL-2 inhibition using Venetoclax has emerged as a promising therapy in Acute Myeloid Leukaemia (AML), but primary and acquired resistance is a main limitation of this treatment. Here, the authors show that the ABC transporter ABCC1 (MRP1) together with glutathione, are associated with Venetoclax resistance and represent potential targets to sensitize AML cells to BCL-2 inhibition.

Using cryo-electron tomography of human T cell leukemia virus type 1 virus-like particles, the authors reveal that the immature Gag lattice is stabilized by the capsid N-terminal domain in contrast to other retroviruses that use the C-terminal domain.

Kodali, Proietti et al. report that increased numbers of P-bodies in leukaemia cells account for sequestration and prevention of tumour-suppressive mRNAs from being translated, which could be targeted as a potential intervention in myeloid leukaemia.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

Viruses trigger potent cytotoxic T cell responses, whereas anti-tumour immunity has been difficult to establish. Here the authors engineer a replicating viral delivery system for tumour-associated antigens, which induces alarmin release, innate activation and protective anti-tumour immunity in mice.

The large and small subunits of the ribosome are synthesized independently within the nucleolus — a membrane-less compartment within the nucleus — before being exported into the cytoplasm. Here, the authors use in situ cryo-ET to observe ribosome maturation and reveal the native organization of the nucleolus.

Neugebauer et al. show activation of the usually silenced embryonic factor DUX4 by herpesviruses in vitro and in patients, and demonstrate that depletion of DUX4 by nanobody degraders abrogates viral replication.

Tight regulation of retrotransposons such as endogenous retroviruses (ERVs) is essential for genome and transcriptome integrity. Here, the authors show that the ATPase function of the chromatin remodeler SMARCAD1 facilitates the binding of KAP1 to ERVs and is required for their repression in embryonic stem cells.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Authors carry out an immunogenetic and virologic analysis of nasopharyngeal and peripheral blood samples, finding that early nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways and reduced systemic inflammation before seroconversion.

Dewald et al. show a high Spike-IgG seroprevalence (95%) in a multicenter study with 1,411 participants. They determined a substantially reduced serum neutralization against the SARS-CoV-2 VOCs BA.4/5 and BQ.1.1. and explored predictive factors of neutralizing activity.

Epidermal homeostasis requires long term stem cell function. Here, the authors apply transcriptional circuitry analysis based on integrated epigenomic profiling of primary human keratinocytes with high and low stem cell function to identify IRF2 as a negative regulator of stemness.

The ability of HIV to alternate between acute and latent forms is thought to rely on a transcriptional feedback loop where polymerase pausing is released by the viral protein Tat. Here, the authors show that viral genome transcription can occur in a burst-like stochastic manner in the absence of Tat.

In leukemia, diverse fusion proteins involving the MLL gene can drive oncogenic activity. Here, the authors describe a dependency of MLL-leukemia cells on the methyltransferase SETD2 to maintain genomic integrity during leukemia initiation and maintenance.

T cell responses specific for HIV-1 Gag peptides increased in HIV-positive recipients of two broadly neutralizing antibodies with prolonged suppression of blood viremia during antiretroviral treatment interruption.

Arrayed CRISPR libraries with each plasmid encoding an array of four non-overlapping single-guide RNAs allow for the efficient genome-wide ablation, activation and epigenetic silencing of human protein-coding genes.

Herpesvirus microRNAs interfere directly with host cell microRNA processing, thereby disrupting mitochondrial architecture, evading intrinsic host defences and driving the switch from latent to lytic infection.