Biology subjects

Schubert, E.

Publications and source records attributed to Schubert, E..

7 recordsLinked to original sources

bioRxiv2026

A novel adenovirus 19K/IX protein promotes infection by preventing proteasomal degradation of tyrosine-ubiquitinated capsid protein pIX

Human adenoviruses (HAdVs) are double-stranded DNA viruses that cause a wide range of diseases, including respiratory, ocular, and gastrointestinal infections. HAdVs rely extensively on alternative splicing to expand their coding capacity and regulate gene expression during infection. Using replication-competent epitope-tagged HAdV-C5 viruses, we investigated the function of the newly identified alternatively spliced viral transcript, 19K/IX, derived from E1B19K and pIX genes. We show that 19K/IX binds to and stabilizes the minor capsid protein IX (pIX), thereby preventing its proteasomal degradation and promoting the production of infectious viral progeny. Mechanistically, we demonstrate that pIX degradation is mediated by a non-canonical ubiquitination of conserved tyrosine residues, which also partially mediate pIX interaction with the PSMC3 subunit of the 26S proteasome. Collectively, these findings identify 19K/IX as a novel regulator of HAdV-C5 infection and suggest that non-canonical tyrosine ubiquitination may represent a mechanism by which HAdV-C5 modulates protein degradation during infection. Author summaryHuman adenoviruses (HAdVs) are clinically important pathogens and widely used as therapeutic tools. Because of their compact genomes, HAdVs use their genetic information very efficiently through alternative pre-mRNA processing. Here, we describe and characterize 19K/IX, a novel fusion protein generated by alternative splicing of two virus genes during infection. We demonstrate that 19K/IX stabilizes the capsid protein IX by preventing its degradation, revealing a previously unrecognized strategy by which HAdVs ensure efficient production of new virus particles. These findings deepen our understanding of HAdV-C5 gene regulation and protein homeostasis and highlight the functional importance of non-canonical viral transcripts.

microbiology↗

bioRxiv2025

Larvicidal activity of Trichoderma atroviride (Hypocreales: Hypocreaceae) against Aedes albopictus (Diptera: Culicidae)

Larviciding is an important part of effective integrated mosquito management. However, growing resistance to chemical and bacterial-based insecticides requires biocontrol agents with novel modes of action. Entomopathogenic fungi are good candidates for larval control due to their capability to infect mosquito larvae and their production of larvicidal compounds. In this study, we isolated a strain of Trichoderma atroviride from Aedes albopictus larvae collected in Manhattan, KS, USA. We used a laboratory-based microcosm assay to expose L3 Ae. albopictus larvae to T. atroviride conidia and culture supernatant treatments. Larvae were monitored daily for survival and development to pupae and adults. In addition, adult survival was monitored for ten-days post pupation, and wing lengths were measured to assess mosquito size. Our results revealed that T. atroviride culture supernatant was a potent larvicide towards Ae. albopictus. However, conidia by themselves were not larvicidal, indicating the major mode of killing was through toxicity exerted by the culture supernatant. We further showed that larval exposure to T. atroviride supernatant delayed larval development to pupae. Sex-specific adult survival was not affected by larval exposure to T. atroviride. However, wing length of male and female mosquitoes were reduced, indicating a reduction in adult mosquito body size as compared to the control. Taken together, this study identifies the culture supernatant from a novel strain of T. atroviride as a potent larvicide of Ae. albopictus, potentially expanding our toolbox for biological control of mosquitoes.

microbiology↗

bioRxiv2023

ZC3H11A interacts with PABPN1 and alters polyadenylation of viral transcripts

Nuclear mRNA metabolism is regulated by multiple proteins, which either directly bind to RNA or form multi-protein complexes. The RNA-binding protein ZC3H11A is involved in nuclear mRNA export, and NF-{kappa}B signaling and is essential during mouse embryo development. Furthermore, previous studies have shown that ZC3H11A is important for nuclear-replicating viruses. However, detailed biochemical characterization of the ZC3H11A protein has been lacking. In this study, we established the ZC3H11A protein interactome in human and mouse cells. We demonstrate that the nuclear poly(A)-binding protein PABPN1 interacts specifically with the ZC3H11A protein and controls ZC3H11A localization into nuclear speckles. We report that ZC3H11A specifically interacts with the human adenovirus type 5 (HAdV-5) capsid mRNA in a PABPN1-dependent manner. Notably, ZC3H11A uses the same zinc finger motifs to interact with PABPN1 and mRNA, with a single zinc finger motif responsible for these functions. Further, we demonstrate that the lack of ZC3H11A alters the polyadenylation of HAdV-5 capsid mRNA. Taken together, our results suggest that the ZC3H11A protein acts as a novel regulator of polyadenylation of nuclear mRNA.

molecular biology↗

bioRxiv2021

Decoding continuous variables from EEG data using linear support vector regression (SVR) analysis with the Decision Decoding Toolbox (DDTBOX)

BackgroundMultivariate classification analysis for event-related potential (ERP) data is a powerful tool for predicting cognitive variables. However, classification is often restricted to categorical variables and under-utilises continuous data, such as response times, response force, or subjective ratings. An alternative approach is Support Vector Regression (SVR), which uses single-trial data to predict continuous variables of interest. New MethodIn this tutorial-style paper, we demonstrate how SVR is implemented in the Decision Decoding Toolbox (DDTBOX). To illustrate in more detail how results depend on specific toolbox settings and data features, we report results from two simulation studies resembling real EEG data, and one real ERP-data set, in which we predicted continuous variables across a range of analysis parameters. ResultsAcross all studies, we demonstrate that SVR is effective for analysis windows ranging from 2 ms - 100 ms, and relatively unaffected by temporal averaging. Prediction is still successful when only a small number of channels encode true information, and the analysis is robust to temporal jittering of the relevant information in the signal. Comparison with existing MethodsOur result show that SVR as implemented in DDTBOX can reliably predict continuous, more nuanced variables, which may not be well-captured by classification analysis. ConclusionsIn sum, we demonstrate that linear SVR is a powerful tool for the investigation of single-trial EEG data in relation to continuous variables, and we provide practical guidance for users.

neuroscience↗

bioRxiv2021

Decoding explicit and implicit representations of health and taste attributes of foods in the human brain

Obesity has become a significant problem word-wide and is strongly linked to poor food choices. Even in healthy individuals, taste perceptions often drive dietary decisions more strongly than healthiness. This study tested whether health and taste representations can be directly decoded from brain activity, both when explicitly considered, and when implicitly processed for decision-making. We used multivariate support vector regression for event-related potentials (as measured by the electroencephalogram) occurring in the first second of food cue processing to predict ratings of tastiness and healthiness. In Experiment 1, 37 healthy participants viewed images of various foods and explicitly rated their tastiness and healthiness, whereas in Experiment 2, 89 healthy participants indicated their desire to consume snack foods, with no explicit instruction to consider tastiness or healthiness. In Experiment 1 both attributes could be decoded, with taste information being available earlier than health. In Experiment 2, both dimensions were also decodable, and their significant decoding preceded the decoding of decisions (i.e., desire to consume the food). However, in Experiment 2, health representations were decodable earlier than taste representations. These results suggest that health information is activated in the brain during the early stages of dietary decisions, which is promising for designing obesity interventions aimed at quickly activating health awareness.

neuroscience↗

bioRxiv2019

Towards the application of Tc toxins as a universal protein translocation system

Tc toxins are large bacterial protein complexes that inject cytotoxic enzymes into target cells using a sophisticated syringe-like mechanism. Tc toxins are composed of a membrane translocator and a cocoon that encapsulates a toxic enzyme. The toxic enzyme varies between Tc toxins from different species and is not conserved. Here, we investigated whether the toxic enzyme can be replaced by other small proteins of different origin and properties, namely human Cdc42, herpes simplex virus ICP47, Arabidopsis thaliana iLOV, Escherichia coli DHFR, human Ras-binding domain of CRAF kinase, and tobacco etch virus protease. Using a combination of electron microscopy, X-ray crystallography and in vitro translocation assays, we demonstrate that it is possible to turn Tc toxins into customizable molecular syringes for delivering proteins of interest across membranes. We also infer the guidelines that protein cargos must obey in terms of size, charge, and fold in order to successfully take advantage of this new universal protein translocation system.

biochemistry↗

bioRxiv2018

Membrane insertion of α-xenorhabdolysin in near-atomic detail

-Xenorhabdolysins (Xax) are -pore-forming toxins (-PFT) from pathogenic bacteria that form 1-1.3 MDa large pore complexes to perforate the host cell membrane. PFTs are used by a variety of bacterial pathogens as an offensive or defensive mechanism to attack host cells. Due to the lack of structural information, the molecular mechanism of action of Xax toxins is poorly understood. Here, we report the cryo-EM structure of the XaxAB pore complex from Xenorhabdus nematophila at an average resolution of 4.0 [A] and the crystal structures of the soluble monomers of XaxA and XaxB at 2.5 [A] and 3.4 [A], respectively. The structures reveal that XaxA and XaxB are built similarly and appear as heterodimers in the 12-15 subunits containing pore. The structure of the XaxAB pore represents therefore the first structure of a bi-component -PFT. Major conformational changes in XaxB, including the swinging out of an amphipathic helix are responsible for membrane insertion. XaxA acts as an activator and stabilizer for XaxB that forms the actual transmembrane pore. Based on our results, we propose a novel structural model for the mechanism of action of Xax toxins.

molecular biology↗