Biology subjects

Grabowski, J.

Publications and source records attributed to Grabowski, J..

4 recordsLinked to original sources

bioRxiv2025

Spatial density and habitat associations of Atlantic Cod on the Northeastern US Continental Shelf

The spatial distribution of the Atlantic cod (Gadus morhua) stock is shaped in part by several habitat and oceanographic variables. In this study, Vector Autoregressive Spatio-Temporal (VAST) models were used to combine data from multiple survey programs to hindcast seasonal spatial densities of three size classes of cod within the Northeast US Continental Shelf from 1982 to 2021. Bottom habitat characteristics, bottom water temperature, depth, and basin-averaged climate indices were included as density covariates. Depth, bottom temperature, and gravel sediments were strongly associated with spatial density. The relative abundance of all size classes generally decreased throughout the time series. Model outputs highlighted patches with persistently high spatial density despite range losses and declining abundance. This aligns with the basin model, a spatial dynamic frequently reported in collapsed fish stocks. The availability of habitat with suitable depth and temperature will likely be reduced under current projections of bottom water temperature, further endangering the recovery of the stock. Improving our understanding of cod habitat preferences and variation in spatial density will be important for future management efforts.

ecology↗

bioRxiv2025

UFMylation promotes orthoflavivirus infectious particle production

Post-translational modifications play crucial roles in viral infections, yet many potential modifications remain unexplored in orthoflavivirus biology. Here we demonstrate that the UFMylation system, a post-translational modification system that catalyzes the transfer of UFM1 onto proteins, promotes infection by multiple orthoflaviviruses including dengue virus, Zika virus, West Nile virus, and yellow fever virus. We found that depletion of the UFMylation E3 ligase complex proteins UFL1 and UFBP1, as well as other UFMylation machinery components (UBA5, UFC1, and UFM1), significantly reduces infectious virion production for orthoflaviviruses but not the hepacivirus, hepatitis C. Mechanistically, UFMylation does not regulate viral RNA translation or RNA replication but instead affects a later stage of the viral lifecycle. We identified novel interactions between UFL1, and several viral proteins involved in orthoflavivirus virion assembly, including NS2A, NS2B-NS3, and Capsid. These findings establish UFMylation as a previously unrecognized post-translational modification system that promotes orthoflavivirus infection, likely through modulation of viral assembly. This work expands our understanding of the post-translational modifications that control orthoflavivirus infection and identifies new potential therapeutic targets. ImportanceOrthoflaviviruses depend on host-mediated post-translational modifications to successfully complete their lifecycle, yet many of these critical interactions remain undefined. Here, we describe a role for a post-translational modification pathway, UFMylation, in promoting infectious particle production of ZIKV and DENV. We show that UFMylation regulates these viruses at a lifecycle stage after initial RNA translation and RNA replication. Additionally, we find that regulation of infection by UFMylation extends to other orthoflaviviruses, including West Nile virus and yellow fever virus, but not to the broader Flaviviridae family. Finally, we demonstrate that UFMylation machinery directly interacts with specific DENV and ZIKV proteins during infection. These studies reveal a previously unrecognized role for UFMylation in regulating orthoflavivirus infection.

microbiology↗

bioRxiv2024

A direct interaction between the RNA-binding proteins Staufen and Tm1-I/C regulates oskar mRNP composition and transport

In the Drosophila female germline, oskar messenger RNA is transported on microtubules from the nurse cells to the posterior pole of the oocyte, where it is translated. Transport of oskar transcripts from the nurse cells into the oocyte requires dynein, while localization of the mRNAs within the oocyte to the posterior pole is dependent upon kinesin-1. Staufen, a dsRNA-binding protein, has been shown to bind the oskar mRNA transport complex in the oocyte and inactivate dynein; however, it remains unclear how kinesin is activated. Here, using surface plasmon resonance, nuclear magnetic resonance spectroscopy and RNA imaging within egg chambers, we demonstrate that Staufen directly interacts with Tm1, a non-canonical kinesin adaptor. This work provides a molecular explanation for the previously unclear role of Staufen in oskar mRNA localization.

molecular biology↗

bioRxiv2024

Sp140L Is a Novel Herpesvirus Restriction Factor

Herpesviruses, including Epstein-Barr Virus (EBV) - a human oncogenic viruses and essential trigger of multiple sclerosis, must bypass host DNA sensing mechanisms to establish lifelong, latent infection. Therefore, herpesviruses encode viral proteins to disrupt key host factors involved in DNA sensing and viral restriction. The first viral latency protein expressed, EBNA-LP, is essential for transformation of naive B cells and establishment of viral gene expression, yet its role in evading host defenses remains unclear. Using single-cell RNA sequencing of EBNA-LP-Knockout (LPKO)- infected B cells, we reveal an antiviral response landscape implicating the speckled proteins as key cellular restriction factors countered by EBNA-LP. Specifically, loss of SP100 or the primate-specific SP140L reverses the restriction of LPKO, suppresses a subset of canonically interferon-stimulated genes, and restores transcription of essential latent viral genes and cellular proliferation. Notably, we also identify Sp140L as a restriction target of the herpesvirus saimiri ORF3 protein, implying a role for Sp140L in immunity to other diverse DNA viruses. This study reveals Sp140L as a restriction factor that we propose links sensing and transcriptional suppression of viral DNA to an IFN-independent innate immune response, likely relevant to all nuclear DNA viruses. Significance StatementHerpesviruses, including the oncogenic Epstein-Barr virus (EBV), are restricted by DNA sensing during initial infection and therefore encode viral proteins to antagonize key restriction factors. We found that the EBV latency protein EBNA-LP, disrupts the speckled proteins Sp100 and Sp140L - an evolutionarily recent protein with unknown function, which we find promotes an anti-viral state that suppresses cellular proliferation, characterized by high induction of cellular anti-viral genes and suppressed transcription of essential viral latency genes. Sp140L also restricts the herpesvirus saimiri, which we find antagonizes Sp140L through the viral protein ORF3. Our study therefore identifies Sp140L as a novel restriction factor of diverse herpesviruses, and likely all DNA viruses, during a critical stage of initial viral infection.

microbiology↗