Biology subjects

Majewska, M.

Publications and source records attributed to Majewska, M..

3 recordsLinked to original sources

bioRxiv2025

Deciphering the Host-Pathogen Interface in COVID-19: The precision molecular insight into epitranscriptomic modifications of high-impact transcripts

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact since its emergence in late 2019. Characterized by a wide spectrum of clinical manifestations, ranging from asymptomatic infection to severe respiratory distress and death, COVID-19 has necessitated extensive research into the host-pathogen interactions that drive disease progression. Understanding the molecular mechanisms underlying the host response to SARS-CoV-2 infection is crucial for the development of effective therapeutic interventions and preventative strategies. This study employed a multi-omic approach that combined direct RNA sequencing (DRS) and Illumina cDNA sequencing to investigate whole blood transcriptomic profiles in COVID-19 patients. By leveraging the unique capabilities of Nanopore DRS, which provides long-read sequencing data, we were able to capture not only gene expression levels but also crucial RNA modifications, including poly(A) tail length, non-adenine residue (non-A), pseudouridylation (psU), and 5-methylcytosine (m5C) methylation. This comprehensive analysis allowed us to identify differentially expressed genes (DEGs) and explore the impact of these RNA modifications on gene expression and function within the context of COVID-19. Our findings reveal significant alterations in gene expression patterns, poly(A) tail lengths, non-A and the prevalence of psU and m5C modifications in COVID-19 patients compared to healthy controls. These results provide valuable insights into the complex interplay between viral infection, host immune response, and RNA processing, contributing to a deeper understanding of COVID-19 pathogenesis.

genetics↗

bioRxiv2024

European Robin Cryptochrome-4a Associates with Lipid Bilayers in an Ordered Manner, Fulfilling a Molecular-Level Condition for Magnetoreception

Since the middle of the 20th century, long-distance avian migration has been known to rely partly on the geomagnetic field. However, the underlying sensory mechanism is still not fully understood. Cryptochrome 4a (ErCry4a), found in European Robin (Erithacus rubecula), a night-migratory songbird has been suggested to be a magnetic sensory molecule. It is sensitive to external magnetic fields via the so-called radical-pair mechanism. ErCry4a is primarily located in the outer segments of the double cone photoreceptor cells in the eye, which contain stacked and highly ordered membranes that could facilitate the anisotropic attachment of ErCry4a needed for magnetic compass sensing. Here, we investigate possible interactions of ErCry4a with a model membrane that mimics the lipid composition of outer segments of vertebrate photoreceptor cells by using experimental and computational approaches. Experimental results show that the attachment of ErCry4a to the membrane could be controlled by the physical state of lipid molecules (average area per lipid) in the outer leaflet of the lipid bilayer. Furthermore, polarization modulation infrared reflection absorption spectroscopy allowed us to determine the conformation, motional freedom, and average orientation of the - helices in ErCry4a in a membrane-associated state. Atomistic molecular dynamics studies supported the experimental results. A [~]1000 kcal mol-1 decrease in the interaction energy as a result of ErCry4a membrane binding was determined compared to cases where no protein binding to the membrane occurred. At the molecular level, the binding seems to involve negatively charged carboxylate groups of the phosphoserine lipids and the C-terminal residues of ErCry4a. Our study reveals a potential direct interaction of ErCry4a with the lipid membrane and discusses how this binding could be an essential step for ErCry4a to propagate a magnetic signal further and thus fulfill a role as a magnetoreceptor.

biophysics↗

bioRxiv2022

FK506-binding protein 2 participates in proinsulin folding

Apart from chaperoning, disulphide bond formation and downstream processing, the molecular sequence of proinsulin folding is not completely understood. Proinsulin requires proline isomerization for correct folding. Since FK506-binding protein 2 (FKBP2) is an ER-resident proline isomerase, we hypothesized that FKBP2 contributes to proinsulin folding. We found that FKBP2 co-immunoprecipitated with proinsulin and its chaperone GRP94, and that inhibition of FKBP2 expression increased proinsulin turnover with reduced intracellular proinsulin and insulin levels. This phenotype was accompanied by an increased proinsulin secretion and the formation of proinsulin high molecular weight complexes, a sign of proinsulin misfolding. FKBP2 knockout in pancreatic {beta}-cells increased apoptosis without detectable upregulation of ER-stress response genes. Interestingly, FKBP2 mRNA was overexpressed in {beta}-cells from pancreatic islets of T2D patients. Based on molecular modelling and an in vitro enzymatic assay, we suggest that proline at position 28 of the proinsulin B chain (P28) is the substrate of FKBP2s isomerization activity. We propose that this isomerization step catalyzed by FKBP2 is an essential sequence required for correct proinsulin folding.

molecular biology↗