Biology subjects

Monier, A.

Publications and source records attributed to Monier, A..

6 recordsLinked to original sources

bioRxiv2026

Pre-existing genome architecture partitions viral takeover in the smallest free-living eukaryote

Nuclear DNA viruses colonize host genomes already structured into complex spatial domains, yet whether established spatial boundaries dictate viral progression remains unresolved--in part because sequence composition and transcriptional output are intertwined in animal models. Here, we tracked productive lytic infection of the marine picoeukaryote Ostreococcus tauri by the giant double-stranded DNA prasinovirus OtV5, recording transcription, accessibility, and 3D contact dynamics across parallel time courses. Although total cellular transcript pools collapsed 18-fold by 10 h post-infection, the host transcriptional shutdown, decay of insulation, early chromatin opening, and viral DNA positioning were all bounded by architectural coordinates defined prior to viral arrival. Across two low-GC outlier domains, chromatin accessibility spiked rapidly, spatial insulation eroded, and loci exhibited relative upregulation by 6 hpi, with the smaller outlier region retaining elevated transcript levels per cell compared to the rest of the genome. Unexpectedly, viral DNA was preferentially depleted from these accessible outlier cores, contacting instead the standard-GC telomeric flanks situated immediately beyond the pre-existing spatial boundaries. Domain identity, rather than local accessibility or active host expression, thus governs viral positioning, demonstrating that pre-existing nuclear architecture partitions the physical and transcriptional takeover of the host cell.

evolutionary biology↗

bioRxiv2025

Cryo-EM reveals multiple mechanisms of ribosome inhibition by doxycycline

Antimicrobial resistance is driving the search for new antibiotics and a greater understanding of their mechanism of action. Doxycycline is amongst the most-prescribed antimicrobials. It demonstrates a particularly low minimum inhibitory concentration against the zoonotic pathogen Coxiella burnetii. Doxycycline canonically targets the bacterial ribosome by blocking tRNA binding at the decoding centre (A-site) of the small subunit. Using cryo electron-microscopy, we analysed doxycycline binding to C. burnetii and Escherichia coli ribosomes. Both structures reveal unexpected binding at the exit tunnel in the large subunit. In C. burnetii three doxycycline molecules stack to block the tunnel. In E. coli one doxycycline molecule triggers a major uncharacterised conformation of the ribosome. This fundamentally reorganises the peptidyl transferase centre and blocks tRNA binding, challenging the concept that this region is largely static. We identify a new ribosomal protein in the C. burnetii large subunit and characterise an additional member of the prokaryotic ribosome hibernation promoting factor family. These insights into ribosome function and antibiotic action may aid the development of new ribosome inhibitor antibiotics.

biochemistry↗

bioRxiv2025

A plasma membrane Ca2+-dependent protein kinase PtCDPK2 promotes phosphorus starvation resilience in Phaeodactylum tricornutum

Phosphorus (P) is an essential element limiting algal growth and productivity in aquatic ecosystems. Diatoms are important microalgae that thrive in nutrient-variable environments. Determining how diatoms perceive and respond to P availability is therefore crucial for understanding their ecological success. P-limited diatoms use a calcium (Ca2+)-dependent signalling pathway to sense and coordinate cellular responses to phosphate resupply. Despite the importance of Ca2+ signalling for diatom environmental sensing, apparatus enabling Ca2+ signal decoding is poorly understood. Here, we characterise the repertoire of an important group of Ca2+ sensor proteins--Ca2+ dependent protein kinases (CDPKs), in Phaeodactylum tricornutum. Several PtCDPKs are transcriptionally upregulated under P starvation. To determine whether PtCDPKs can coordinate P-starvation responses or act to transduce Ca2+ signals induced by P resupply, we functionally characterised PtCDPK2. PtCDPK2 is highly expressed in P-limited cells and localises to the cell periphery, suggesting a role regulating plasma membrane processes. Further, PtCDPK2 is co-regulated with the transcriptional regulator of P-starvation responses, PtPSR1. PtCDPK2 expression is also coordinated with the induction of P-Ca2+ signalling, which is driven by depletion of cellular P rather than external P exhaustion, or growth limitation. Ptcdpk2 mutants have significantly reduced photosynthetic efficiency and alkaline phosphatase activity under P starvation, but we do not find evidence for a direct role coordinating downstream responses to P resupply. These findings suggest PtCDPK2 is essential for regulating P-starvation physiology and reveals a role for Ca2+-signalling apparatus in promoting diatom tolerance in low P environments.

cell biology↗

bioRxiv2025

Insulated Outlier Chromosomes Drive Metabolic and Evolutionary Innovation in Minimal Eukaryotic Algae

Marine picoeukaryotes of the order Mamiellales, including Ostreococcus tauri, the smallest known free-living eukaryote, possess compact genomes yet maintain enigmatic "outlier chromosomes" characterised by lower GC content and hypervariability. To determine the structural and functional nature of these regions, we applied chromosome conformation capture to O. tauri and conducted comparative multi-omics analyses across the Mamiellales order, presenting the first analysis of three-dimensional genome organisation in marine picoeukaryotes. We reveal that outlier regions form structures resembling topologically associating domains, with sharp boundaries that spatially insulate them from the standard chromosomes. These compartments are defined by a distinctive chromatin state characterised by hypomethylation and transcriptional hyperactivity, and are frequently, though not universally, enriched in transposable elements. Crucially, species that lack transposable element enrichment in their outlier chromosomes nonetheless retain the transcriptional hyperactivity and distinct nucleotide composition of these regions, indicating that the functional identity of these compartments persists independently of transposon accumulation. The dynamic nature of these insulated domains is highlighted by the presence of structurally diverse giant polyketide synthase loci. We identify convergent genomic organisation in other chlorophytes, as well as phylogenetically distant stramenopiles. Our results suggest that such compartmentalisation of rapidly evolving, dynamic genomic regions represents a fundamental architectural principle of minimal eukaryotic genomes.

evolutionary biology↗

bioRxiv2025

Metagenomics of the MAST-3 stramenopile, Incisomonas, and its associated microbiome reveals unexpected metabolic attributes and extensive nutrient dependencies

Protists are polyphyletic singled-celled eukaryotes that underpin global ecosystem functioning, particularly in the oceans. Most remain uncultured, limiting investigation of their physiology and cell biology. MArine STramenopiles (MASTs) are heterotrophic protists that, although related to well-characterised photosynthetic diatoms and parasitic oomycetes, are poorly studied. The Nanomonadea (MAST-3) species Incisomonas marina has been maintained in co-culture with a bacterial consortium, offering opportunities to investigate the metabolic attributes and nutritional dependencies of the community. Employing a metagenomics approach, the 68 Mbp haploid genome of I. marina was retrieved to an estimated completeness of 93%, representing the most complete MAST genome so far. We also characterised the diversity of, and assembled genomes for, 23 co-cultured bacteria. Auxotrophy of I. marina for B vitamins (B1, B2, B6, B7 and B12), but not vitamins C, B3, B5 and B9 was predicted. Several bacteria also lacked complete B-vitamin biosynthesis pathways, suggesting that vitamins and/or their precursors are exchanged in the consortium. Moreover, I. marina lacked the ability to synthesise half the protein amino acids, although genes encoding the complete urea cycle were identified, like diatoms; this may play a role in recycling organic nitrogen compounds. Unexpectedly, we also identified the gene DSYB for dimethylsulphoniopropionate (DMSP) biosynthesis. Biosynthesis of this important stress-protectant and bacterial chemoattractant is typically found in photosynthetic eukaryotes and has not before been identified in heterotrophic stramenopiles. Together, our study reveals the metabolic attributes of a hitherto understudied organism, advancing knowledge of the evolution and adaptations of the stramenopiles and informing future culturing efforts.

microbiology↗

bioRxiv2021

ZC3H4 restricts non-coding transcription in human cells

The human genome encodes thousands of non-coding RNAs. Many of these terminate early and are then rapidly degraded, but how their transcription is restricted is poorly understood. In a screen for protein-coding gene termination factors, we identified ZC3H4. However, its depletion causes upregulation and extension of hundreds of unstable transcripts, particularly antisense RNAs and those transcribed from so-called super-enhancers. These loci are occupied by ZC3H4, suggesting that it directly functions in their transcription. Consistently, engineered tethering of ZC3H4 to reporter RNA promotes its degradation by the exosome. ZC3H4 is metazoan-specific - interesting when considering its impact on enhancer RNAs that are less prominent in single-celled organisms. Finally, ZC3H4 loss causes a substantial reduction in cell proliferation, highlighting its overall importance. In summary, we identify ZC3H4 as a factor that plays an important role in restricting non-coding transcription in multi-cellular organisms.

molecular biology↗