Biology subjects

Chevreux, G.

Publications and source records attributed to Chevreux, G..

At least 19 recordsLinked to original sources

bioRxiv2026

Cyclin B phosphorylation by PKA safeguards the G2-arrest in vertebrate oocytes

Entry into meiotic M-phase in vertebrate oocytes requires activation of Cdk1-Cyclin B, which is restrained by the cAMP-PKA signalling during prophase arrest. Although Cdc25C and ARPP19 are established PKA substrates in this context, they do not fully explain how PKA represses Cdk1 activation. Here we used Turbo-ID approach using catalytic PKA (PKAc) as the bait to identify substrates in Xenopus laevis oocytes. Unexpectedly, this screen identified Cyclin B2, the regulatory subunit of Cdk1, as a PKA-proximal protein. Although Cyclin B2 does not stably associate with PKAc, it harbors a conserved PKA motif around Serine 271 within Cyclin Box 2. We show that PKAc phosphorylates Cyclin B2 at S271 both in vivo and in vitro. Functionally, a phosphomimic Cyclin B2 mutant at this site fails to induce meiotic maturation and Cdk1 activation. S271 phosphorylation neither alters Cyclin B2 stability nor its binding to Cdk1 in vivo. S271 phosphorylation does not impair Cdk1 activity toward a single-site substrate, such as PP1, but slows Cyclin-B-dependent multisite phosphorylation of Cdc25C, a key regulator of the Cdk1 activation network. These findings identify Cyclin B as a direct and conserved PKA target, revealing the mechanistic link between PKA activity and Cdk1-Cyclin B repression that maintains oocyte prophase arrest.

cell biology↗

bioRxiv2026

Low-input proteomics enables proteome and phosphoproteome-scale molecular phenotyping of separase-deficient oocytes

We performed a comprehensive quantitative proteomic analysis of mouse oocytes using as few as 40 oocytes per condition, comparing wild-type and separase knockout oocytes at metaphase I and metaphase II. To this end, we generated a deep proteomic library spanning oocyte cell cycle stages, enabling the identification of numerous phosphosites without phosphopeptide enrichment. We further combined data-dependent (DDA) and data-independent (DIA) acquisition strategies, analyzed through multiple software pipelines in both library-based and library-free modes. Our results reveal extensive proteome remodeling during the metaphase I to metaphase II transition in wild-type oocytes, consistent with dynamic regulation of meiotic processes. As a proof of concept for our workflow, we asked whether separase knockout oocytes--unable to separate chromosomes in meiosis I--progress into meiosis II. Direct comparison of wild-type and separase knockout oocytes at the metaphase II stage revealed minimal global differences, supporting the idea that both conditions converge toward a comparable metaphase II-like cellular state despite distinct chromosomal configurations. However, at a finer scale, specific alterations were detected among chromosome-associated proteins. Notably, Meikin was enriched in separase-deficient metaphase II oocytes, consistent with defective separase-dependent cleavage and subsequent turnover. More broadly, several proteins involved in chromosome organization displayed behavior similar to Meikin, suggesting that separase activity regulates multiple substrates to orchestrate chromosome segregation during female meiosis.

Cell Biology↗

bioRxiv2026

An RNA-centric interactomics screen identifies novel proviral and antiviral genome binding interactors for tick-borne encephalitis virus

The tick-borne encephalitis virus (TBEV), which belongs to the Orthoflavivirus genus, is a medically significant arbovirus in Europe and Asia. Despite distinct pathobiological outcomes, arboviruses have evolved specific strategies to co-opt cellular factors for replication and immune evasion, that involve both viral proteins and viral RNA. The RNA genome of TBEV, as both the substrate for genome replication and translation and a designated target for innate antiviral immunity, is a nexus for interactions with the proteome of host cells. Nonetheless, the molecular bases of these interactions and their implications for the replicative cycle of TBEV remain poorly understood. To create an inventory of such interactions and gain understanding of their functional import, we have resolved the set of cellular proteins bound to TBEV RNA in infected human cells using an agnostic RNA-centric approach. Functional annotation of the resulting core interactome of 215 human host factors showed that viral RNA is deeply embedded in multiple cellular pathways, including those related to RNA and protein metabolism, cytoskeletal scaffolding, vesicle trafficking and innate antiviral immunity. For selected human interactors, we addressed their impact on TBEV infection in gene knockdown experiments, thereby identifying multiple restriction and dependency factors. These included sensors and effectors of innate immune pathways, as well as epitranscriptomic modifiers. Among the former, the dynamin-like GTPase MX2 protein, an interferon-stimulated gene with antiviral activity against multiple viruses including mosquito-borne orthoflaviviruses, displayed unexpected proviral activity against TBEV and a second tick-borne orthoflavivirus. Among the latter, WDR4, the non-catalytic component of the METTL1-WDR4 methyltransferase complex, emerged as a restriction factor with broad-spectrum activity against arboviruses belonging to multiple families of positive-strand RNA viruses. In conclusion, this first description of the RNA interactome of a tick-borne orthoflavivirus illuminates the molecular interactions that underpin TBEV infection of human cells, which taken together reflect both the common ancestry of tick- and mosquito-borne orthoflaviviruses and their considerable evolutionary divergence.

molecular biology↗

bioRxiv2026

Molecular dialogue between Orthonairovirus and tick: RNA-protein interactome of Hazara virus, a BSL2 model of Crimean-Congo Hemorrhagic Fever virus, in Hyalomma cells

Climate change and ecosystem collapse promote geographic expansion of vector-borne diseases, as witnessed by the recent incursions into Spain of the virus responsible for Crimean-Congo hemorrhagic fever (CCHFV). CCHFV is maintained in a tick-vertebrate cycle, principally involving ticks of the genus Hyalomma. Faced with the spread of Hyalomma ticks, and therefore the threat of a natural introduction of CCHFV into Western Europe, appropriate surveillance tools and control measures need to be implemented. It is both within and by the tick that CCHFV is maintained and spread in the environment. Despite prolonged portage of the virus, the tick is not overtly affected by CHFV infection. One of the prerequisites in conceiving control strategies is to understand the molecular mechanisms that intimately link the virus to its arthropod host. Despite the central role of the tick in the biology of CCHFV, these mechanisms are ill-defined, owing in part to the constraints associated with handling CCHFV-infected ticks in biosafety level 4 containment. In this study, we established the network of interactions between the S segment of the RNA genome Hazara virus (HAZV), a BSL-2 model of CCHFV, and Hyalomma proteins using ChIRP-MS technique. We identified 166 tick proteins, 21 of which have been described as RNA-binding proteins. Gene ontology and pathway enrichment analyses revealed that the S segment RNA interacts predominantly with mitochondrial proteins that belong to various mitochondrial metabolic pathways.

microbiology↗

bioRxiv2025

Regulation of cell proliferation by a novel feedback system on Cdk function

The proliferation of eukaryotic cells is regulated by a complex network of regulatory systems that promotes efficient cell cycle progression and ensures proper responses to the environment. Despite this complexity, the core inputs that are necessary and sufficient for robust alternation of DNA replication and mitosis are surprisingly simpler than anticipated. Indeed, fission yeast cells operating with an engineered minimal cell cycle network that lacks the highly conserved Wee1+Cdc25 feedback loops on Cdk1 function are viable, although slow growing. This provides a unique entry for evaluating how such simplified cells can evolve and improve their proliferation potential while exploring unknown mechanisms modulating cell cycle progression. Taking advantage of this model, we applied laboratory evolution assays to minimal fission yeast backgrounds and selected for the emergence of faster growing populations. We found that loss of the small disordered protein Spo12 brings about enhanced population growth in cells lacking the Wee1+Cdc25 mitotic switch. Importantly, we demonstrate that Spo12 defines a new and conserved family of inhibitors of the Cdk-counteracting phosphatase PP2A that are directly regulated by Cdk-dependent phosphorylation. Our results also reveal a trade-off associated with Spo12-dependent regulation, which may have implications for our understanding of the principles underlying the evolution of cell cycle control. Finally, our study highlights how combining simplified circuits with experimental evolution allows for uncovering regulatory elements that may be obscured by network complexity.

cell biology↗

bioRxiv2025

EMILIN1 emerges as a TGFbeta/SETDB1-regulated secreted biomarker in Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is an incurable muscle-wasting disorder characterized by chronic membrane damage, inflammation, and progressive fibrosis. Fibrosis in DMD is driven by sustained TGF{beta} signaling, which promotes extracellular matrix (ECM) accumulation. We previously showed that SETDB1 sustains the TGF{beta}-induced fibrotic response in DMD myotubes. Here, we further show that SETDB1 modulates the TGF{beta}-induced secretome, particularly by regulating ECM-related proteins. Comparison of the basal secretome from DMD patient-derived myotubes and healthy controls revealed a distinct disease-specific profile. Integrating both secretome analyses, we identified EMILIN1, an ECM glycoprotein not previously studied in skeletal muscle, as a robust shared candidate; EMILIN1 is enriched in the DMD secretome, further upregulated by TGF{beta}, and downregulated upon SETDB1 depletion. We confirmed EMILIN1 overexpression in DMD patient muscle biopsies, validating its pathological relevance. Functionally, EMILIN1 depletion modulated myogenic differentiation and reduced expression of the fibrotic marker SERPINE1. These findings establish EMILIN1 as a novel secreted regulator of myogenesis and fibrosis, and implicate SETDB1 in shaping the TGF{beta}-dependent secretome in DMD. Our integrative proteomic approach provides new insights into the molecular drivers of impaired regeneration in DMD and highlights potential therapeutic targets.

genetics↗

bioRxiv2025

Greatwall depletion from Xenopus oocytes reveals a key role of the cyclin B/CDK1-PP2A-B55 balance in the coordination of meiotic events

Meiotic progression relies on maintaining a precise balance between cyclin B/CDK1 activity and the phosphatase PP2A-B55. The latter is negatively regulated by the Greatwall kinase (Gwl). In Xenopus oocytes, we show that the loss of Gwl and the subsequent hyperactivation of PP2A-B55 severely disrupt the transition from meiosis I to meiosis II. This disruption prevents phosphorylation of both Wee1/Myt1 and the APC/C complex, thereby blocking APC/C activation. As a consequence, APC/C remains inactive during the MI-MII transition, which impairs cyclin degradation and the partial CDK1 inactivation that is normally required at this stage. Additionally, the mos-MAPK-Rsk1/2 pathway fails to activate due to insufficient Mos accumulation, thereby preventing metaphase II arrest. Finally, the lack of APC/C activation during meiosis I inhibits the degradation of its inhibitor Erp1, revealing a critical feedback loop between APC/C and Erp1. Overall, our findings reveal that Gwl is a key coordinator of both meiotic divisions, acting through dual regulation of APC/C and the Mos/MAPK/Rsk1/2 pathways by modulating PP2A-B55 activity.

biochemistry↗

bioRxiv2025

A developmental condensin I complex assists the Paramecium PiggyMac domesticated transposase during programmed DNA elimination

Prokaryotes and eukaryotes use diverse strategies to cope with invading mobile genetic elements, including programmed DNA elimination (PDE). In the ciliate Paramecium, elimination of transposable elements and their relics requires the PiggyMac (Pgm) endonuclease and its five PgmL partners, yet how this machinery is targeted to cleavage sites remains unclear. Here, we identified condensin I subunits in the proximity proteomes of Pgm and PgmL4. We show that they belong to a condensin complex that is essential for PDE and localizes to developing somatic nuclei. Depleting the development-specific subunits of this complex blocks DNA elimination, phenocopying a Pgm depletion. Developmental condensin is required for the correct nuclear localization of Pgm and some of the PgmLs. Moreover, Pgm and these PgmLs co-immunoprecipitate with condensin I. Our findings uncover functional and physical interactions between a eukaryotic DNA cleavage machinery and a specialized condensin complex that is critical for PDE in a non-dividing nucleus.

molecular biology↗

bioRxiv2025

A genetic screen reveals a key role for Reg1 in 2-deoxyglucose sensing and yeast AMPK inhibition

The yeast Saccharomyces cerevisiae thrives in sugar-rich environments by rapidly consuming glucose and favoring alcoholic fermentation. This metabolic strategy is tightly regulated by glucose signaling pathways, particularly the glucose repression pathway, which prevents the expression of genes required for the utilization of alternative carbon source. Central to this regulatory network is the yeast ortholog of the heterotrimeric 5'AMP-activated protein kinase (AMPK), which adjusts gene expression in response to glucose availability. The activity of the yeast AMPK complex is primarily regulated by the phosphorylation state of its catalytic subunit Snf1, a process orchestrated by a balance between upstream kinases and phosphatases. Among the latter, the Protein Phosphatase 1 (PP1) complex Reg1/Glc7 plays a critical role in repressing Snf1 activity under glucose-rich conditions. Despite its importance, the precise mechanism by which glucose availability leads to Snf1 inhibition remains incompletely understood. Evidence suggests that hexokinase 2 (Hxk2) participates in this pathway, potentially coupling the early steps of glucose metabolism to Snf1 signaling. Notably, the toxic glucose analog 2-deoxyglucose (2DG)- which is phosphorylated by Hxk2 but not further metabolized-mimics glucose in its ability to repress Snf1, implicating glucose or 2DG phosphorylation as a key regulatory signal. In this study, we explore the molecular basis of 2DG resistance in yeast through a large-scale genetic screen. The identified mutations confer resistance either by reducing 2DG phosphorylation (e.g., mutations in HXK2) or by enhancing constitutive Snf1 activity, via gain-of-function alleles in AMPK subunits or loss-of-function mutations in REG1 and GLC7. We describe a novel class of REG1 missense mutations, including reg1-W165G, that maintain normal basal Snf1 activity but fail to mediate 2DG-induced Snf1 inhibition, rendering cells effectively immune to 2DG toxicity. These findings position Reg1 as a central mediator in glucose sensing and further suggest that 2DG toxicity primarily results from aberrant Snf1 inactivation rather than a direct metabolic disturbance.

cell biology↗

bioRxiv2025

PARP inhibitors affect the replisome and replication fork progression during a single S phase.

Poly(ADP-ribosyl)ation (PARylation) is a protein modification mostly synthesised and degraded by PARP1/2 and PARG enzymes, respectively. PARylation is involved in many covalent and non-covalent protein-protein interactions in the nucleus, making it a powerful form of molecular signaling in DNA metabolism. PARP inhibitors (PARPi) have shown efficacy in the treatment of Homologous Recombination (HR)-deficient cancers, yet the full range of molecular mechanisms underlying the activity of these drugs is not fully understood. Here, we decipher the direct consequences of PARPi-induced loss of PARylation on DNA replication. First, PARPi treatment during a single S phase induces replicative stress, delays S phase progression and causes genome-wide replication timing changes of disease-associated regions. These DNA replication alterations appear to be caused by an accumulation of SSBs in the DNA replicative template when PARylation is inhibited, which then seems to lead to one-ended DSBs and fork collapse during S phase. Second, PARPi deplete FANCD2-I, BRCA, monoubiquitinated PCNA and RAD18 proteins from the replisomes. The two PARPi tested then appear to modulate the choice of fork restart mechanisms and influence replisome dynamics in different ways. Taken together, our study highlights the common and unique primary effects of two PARPi on unperturbed DNA replication in human cells. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=169 SRC="FIGDIR/small/639283v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@298f8dorg.highwire.dtl.DTLVardef@8f8cbcorg.highwire.dtl.DTLVardef@60952forg.highwire.dtl.DTLVardef@e2700a_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Large extracellular vesicles containing mitochondria (EVMs) derived from Alzheimer disease cells harbor pathologic functional and molecular profiles and spread mitochondrial dysfunctions

In addition to small extracellular vesicles known as exosomes, cells release large extracellular vesicles containing mitochondria (EVMs). However, the molecular and functional characteristics of EVMs, as well as the impact of EVM secretion on the spreading of mitochondrial dysfunction between cells, remain unknown in the context of Alzheimers Disease (AD). Here, we provide an ultrastructural, biochemical, and functional characterization of EVMs isolated from cells expressing the amyloid precursor protein (APP) with the familial Swedish mutation (APPswe). We identified differential proteomic and lipidomic signatures in APPswe-derived EVMs compared to control EVMs and revealed a specific proteomic profile in EVMs isolated from conditioned media of fibroblasts from AD patients at the prodromal stage of the disease. Our findings show that APP-C terminal fragments (APP-CTFs) pathogenic accumulation in cells potentiates EVM secretion through the budding of the plasma membrane. We lastly demonstrated that APP-CTFs loaded EVMs are active carriers of dysfunctional mitochondria that transfer mitochondrial pathology to naive control recipient cells.

neuroscience↗

bioRxiv2024

Different alterations in mRNP composition trigger an increase in harmful R-loops

Understanding how the assembly of nascent mRNA into a ribonucleoprotein (mRNP) influences R-loop homeostasis is crucial for gaining insight into the cellular mechanisms that prevent genome instability. Here, we identify three RNA-binding proteins, Rie1, Rim4 and She2, whose stoichiometry is important to limit R-loop accumulation and, thus, to prevent DNA damage. Interestingly, Rim4 and She2 are overrepresented in mRNPs assembled in the absence of THO. In addition, we found that an excess of Dis3 impairs exosome function, promoting R-loops, particularly from non-coding RNAs, which cause genomic instability. Our results indicate that mRNP assembly is a precise process that, when perturbed by changes in the availability of different RBPs or RNAs, causes R-loop-mediated DNA damage in the cell. These results may help to understand the mechanism that promotes cancer, as several RBPs are overexpressed in different types of tumors. Author summaryR-loops are three-stranded structures formed by a DNA-RNA hybrid and the displaced ssDNA. The accumulation of R-loops damages the genome, highlighting the need for their tight regulation. One of the mechanisms that prevents R-loop formation is the co-transcriptional assembly of the nascent RNA into a messenger ribonucleoprotein (mRNP). Our study reveals that mRNP biogenesis is highly sensitive to perturbations. Not only the absence of mRNP components, but also the overexpression of specific RNA-binding proteins (RBPs) or the persistence of unstable transcripts, significantly stresses mRNP assembly, resulting in R-loop accumulation and consequent DNA damage. R-loops are involved in a number of neurodegenerative diseases and cancer, highlighting the importance of understanding the cellular processes that mitigate their accumulation.

genetics↗

bioRxiv2024

Annulate Lamellae biogenesis is essential for nuclear pore function

Nuclear pore complexes (NPCs) enable nucleocytoplasmic transport. While NPCs primarily localize to the nuclear envelope (NE), they also appear in cytoplasmic endoplasmic reticulum (ER) membranes called annulate lamellae (AL). Though discovered in the mid-20th century, ALs function and biogenesis remain unclear. Previously considered exclusive to embryonic and malignant cells, we find AL in somatic mammalian cells. Under normal conditions, AL store pre-assembled NPCs (AL-NPCs) that integrate into the NE during G1 to support nuclear expansion. Upon pathological stimuli, AL transfer to the NE is impaired, leading to their cytoplasmic accumulation. RanBP2 (Nup358) is essential for AL biogenesis, with its phenylalanine-glycine (FG) repeats promoting AL-NPC scaffold oligomerization. ER-associated Climp63 (CKAP4) directs AL-NPCs to ER sheets and the NE. This AL-driven nuclear pore formation is complementary to the canonical routes, constituting a distinct NPC assembly pathway. Our work uncovers the biogenesis mechanism of AL and the nuclear function of this key cellular organelle.

cell biology↗

bioRxiv2024

Cell cycle-dependent mRNA localization in P-bodies

Understanding the dynamics of RNA targeting to membraneless organelles is essential to disentangle their functions. Here, we investigate how P-bodies (PBs) evolve during cell cycle progression. PB purification across the cell cycle uncovers widespread changes in their RNA content, which are partly uncoupled from cell cycle-dependent changes in RNA expression. Single molecule FISH shows various mRNA localization patterns in PBs peaking in G1, S, or G2, with examples illustrating the timely capture of mRNAs in PBs when their encoded protein becomes dispensable. Yet, rather than directly reflecting absence of translation, cyclic mRNA localization in PBs can be controlled by RBPs, such as HuR in G2, and by RNA features. Indeed, while PB mRNAs are AU-rich at all cell cycle phases, they are specifically longer in G1, possibly related to post-mitotic PB reassembly. Altogether, our study supports a model where PBs are more than a default location for excess untranslated mRNAs.

cell biology↗

bioRxiv2024

Missense mutation in the activation segment of the kinase CK2 models Okur Chung neurodevelopmental disorder and alters the hippocampal glutamatergic synapse

Exome sequencing has enabled the identification of causative genes of monogenic forms of autism, amongst them, in 2016, CSNK2A1, the gene encoding the catalytic subunit of the kinase CK2, linking this kinase to Okur-Chung Neurodevelopmental Syndrome (OCNDS), a newly described neurodevelopmental condition with many symptoms resembling those of autism spectrum disorder. Thus far, no preclinical model of this condition exists. Here we describe a knockin mouse model that harbors the K198R mutation in the activation segment of the kinase. This region is a mutational hotspot, representing one-third of patients. These mice exhibit behavioral phenotypes that mirror patient symptoms. Homozygous knock-in (KI) mice die mid-gestation while heterozygous KI mice are born at half of the expected mendelian ratio and are smaller in weight and size than wildtype littermates. Heterozygous KI mice showed alterations in cognition and memory-assessing paradigms, enhanced stereotypies, altered circadian activity patterns, and nesting behavior. Phosphoproteome analysis from brain tissue revealed alterations in the phosphorylation status of major pre- and postsynaptic proteins of heterozygous KI mice. In congruence, we detect reduced synaptic maturation in hippocampal neurons and attenuated long-term potentiation in the hippocampus of KI mice. Taken together, K198R KI mice exhibit significant face validity, presenting ASD-relevant phenotypes, synaptic deficits and alterations in synaptic plasticity, all of which strongly validate this line as a mouse model of OCNDS.

neuroscience↗

bioRxiv2023

Qualitative rather than quantitative phosphoregulation shapes the end of meiosis I in budding yeast

Exit from mitosis is brought about by dramatic changes in the phosphoproteome landscape. A drop in Cyclin-dependent kinase (Cdk), the master regulatory kinase, and activation of counteracting phosphatases such as Cdc14 in budding yeast, results in ordered substrate dephosphorylation, allowing entry into a new cell cycle and replication licensing. In meiosis however, two cell divisions have to be executed without intermediate DNA replication, implying that global phosphorylation and dephosphorylation have to be adapted to the challenges of meiosis. Using a global time-resolved phosphoproteomics approach in budding yeast, we compared the phosphoproteome landscape between mitotic exit and the transition from meiosis I to meiosis II. We found that unlike exit from mitosis, Cdk phosphomotifs remain mostly stably phosphorylated at the end of meiosis I, whereas a majority of Cdk-unrelated motifs are reset by dephosphorylation. However, inducing an artificial drop of Cdk at metaphase of meiosis I leads to ordered substrate dephosphorylation, comparable to mitosis, indicating that phosphoregulation of substrates at the end of meiosis I is thus mainly qualitatively rather than quantitatively ordered.

cell biology↗

bioRxiv2023

The nuclear PIWI-interacting protein Gtsf1 controls the selective degradation of small RNAs in Paramecium

Ciliates undergo developmentally programmed genome elimination, in which small RNAs direct the removal of target DNA segments, including transposable elements. At each sexual generation, the development of the macronucleus (MAC) requires massive and reproducible elimination of a large proportion of the germline micronuclear (MIC) genome, leading to a highly streamlined somatic MAC genome. 25-nt long scnRNAs are produced from the entire germline MIC genome during meiosis, and this initial complex small RNA population is then transported to the maternal MAC, where selection of scnRNAs corresponding to germline (MIC)-specific sequences is thought to take place. Selected scnRNAs, loaded onto the PIWI protein Ptiwi09, guide the deposition of histone H3 post-translational modifications (H3K9me3 and H3K27me3) onto transposable elements in the developing macronucleus, ultimately triggering their specific elimination. How germline-specific MIC scnRNAs are selected remains to be determined. Here, we provide important mechanistic insights into the scnRNA selection pathway by identifying a Paramecium homolog of Gametocyte specific factor 1 (Gtsf1) as essential for the selective degradation of scnRNAs corresponding to retained somatic MAC sequences. Consistently, we also show that Gtsf1 is exclusively localized in the maternal macronucleus and associates with the scnRNA-binding protein Ptiwi09. Furthermore, Gtsf1 is necessary for DNA elimination and correct H3K9me3 and H3K27me3 localization in the new developing macronucleus, demonstrating that the scnRNA selection process is important for genome elimination. We propose that Gtsf1 is required for the coordinated degradation of Ptiwi09-scnRNA complexes that pair with nascent RNA transcribed from the maternal MAC genome, similarly to the mechanism suggested for microRNA target-directed degradation in metazoans.

genetics↗

bioRxiv2023

Mechanisms of Nuclear Pore Complex disassembly by the mitotic Polo-Like Kinase 1 (PLK-1) in C. elegans embryos

The nuclear envelope, which protects and organizes the interphase genome, is dismantled during mitosis. In the C. elegans zygote, nuclear envelope breakdown (NEBD) of the parental pronuclei is spatially and temporally regulated during mitosis to promote the unification of the parental genomes. During NEBD, Nuclear Pore Complex (NPC) disassembly is critical for rupturing the nuclear permeability barrier and removing the NPCs from the membranes near the centrosomes and between the juxtaposed pronuclei. By combining live imaging, biochemistry, and phosphoproteomics, we characterized NPC disassembly and unveiled the exact role of the mitotic kinase PLK-1 in this process. We show that PLK-1 disassembles the NPC by targeting multiple NPC sub-complexes, including the cytoplasmic filaments, the central channel, and the inner ring. Notably, PLK-1 is recruited to and phosphorylates intrinsically disordered regions of several multivalent linker nucleoporins, a mechanism that appears to be an evolutionarily conserved driver of NPC disassembly during mitosis. (149/150 words) One-Sentence SummaryPLK-1 targets intrinsically disordered regions of multiple multivalent nucleoporins to dismantle the nuclear pore complexes in the C. elegans zygote.

cell biology↗