Biology subjects

Rommel, M.

Publications and source records attributed to Rommel, M..

3 recordsLinked to original sources

bioRxiv2026

Non-translated mRNA levels determine P-body properties

Translational repression enables rapid adaptation to environmental changes. Under stress, translational repressed mRNA and mRNA decay factors accumulate in cytoplasmic processing bodies (PBs), implicated in mRNA storage and decay. PBs have been mostly studied under glucose starvation in yeast, yet, knowledge is limited under other stress conditions. Here, we identify a correlation between the level of translation attenuation and the number, brightness, fluidity and recruitment of PB core components. Stresses triggering strong translation attenuation caused the formation of few bright and more fluid PBs that recruit the decay factors en bloc. Conversely, weaker translation attenuation induced numerous, dim, more viscous PBs to which PB proteins were sequentially recruited. Importantly, increasing non-translated mRNA levels augmented the brightness of dim PBs and accelerated decay machinery recruitment. Finally, boosting RNA levels increased the size of Dhh1 helicase-containing droplets in vitro. Taken together, we propose a model in which the assembly pathway and biophysical properties of PBs are governed by non-translated mRNA abundance. TeaserBiophysical properties, protein composition and assembly pathways of processing bodies are dependent on available mRNA levels.

cell biology↗

bioRxiv2025

Perinatal Nicotine Exposure Disrupts Hematopoietic Stem Cell Development and Elevates Influenza Susceptibility in Adulthood

Tobacco use during pregnancy has many deleterious health consequences for not only the smoking mother, but also on the unborn fetus. Children of smoking mothers are reported to have higher frequency and severity of respiratory diseases later in life; however, the mechanisms driving this increased vulnerability are not clearly understood. One potential cause of increased disease susceptibility is an altered immune system, originating in epigenetically maladaptive hematopoietic stem cells (HSCs). Here, we show that perinatal nicotine exposure (PNE) alters the establishment of HSCs and fetal-derived non-traditional tissue immune cells, with no alterations in circulating immune cell numbers. Suppression of HSCs and lung immune cells persisted for weeks after PNE had ceased. Strikingly, PNE led to increased disease susceptibility and severity upon challenge with influenza A virus in adulthood. This was associated with significant and highly selective alterations in lung immune cells, emphasizing the importance of cellular mechanisms in resilience to infections. Together, these experiments demonstrate that perinatal exposures that have deleterious consequences on hematopoietic establishment can impair immune function for life and identify the cellular mechanisms by which perinatal nicotine exposure predisposes the offspring to a weakened defense against respiratory pathogens. HIGHLIGHTSO_LIPerinatal nicotine exposure (PNE) causes long-term alterations of hematopoiesis C_LIO_LIPNE perturbs hematopoietic stem cell (HSC) development and maintenance C_LIO_LIPNE diminishes the population of fetal-derived tissue-resident alveolar macrophages C_LIO_LIPNE alters cellular mechanisms, exacerbating disease severity later in life C_LIO_LINicotine suppression of central immunity is manifested mechanistically by altered immune cell output C_LI

developmental biology↗

bioRxiv2022

Non-neutralizing antibody responses to vesicular stomatitis virus-vectored influenza A virus vaccines correlate with protection

Seasonal influenza virus infections remain a major global public health burden. In addition, influenza A virus (IAV) exhibits high pandemic potential through zoonotic spread from avian hosts to humans. Currently licensed IAV vaccines are mainly directed against the immuno-dominant surface protein hemagglutinin (HA). Since HA is antigenically highly variable, IAV can escape vaccine-derived immunity through antigenic drift. However, vaccine preparations such as the live-attenuated influenza vaccine (LAIV) also contain other more conserved viral antigens, whose contribution to influenza immunity are not fully elucidated. To determine the extent to which conserved LAIV antigens contribute to establishing protective immunity against heterologous IAV strains, we generated vesicular stomatitis virus-based single-round vector vaccines expressing individual LAIV antigens, and tested their ability to protect mice from a heterologous challenge with two IAV strains, PR8[H1N1] and rSC35M[H7N7]. We found that immunization with nucleoprotein (NP), ion channel M2, and the stem-region of HA (HAstem), but not matrix protein (M1), provide protection from severe disease caused by either IAV strain. This effect correlated with development of non-neutralizing antibodies cross-reactive with both virus strains. Notably, the individual antigens induced specific IgG subclass profiles with different reactivity against PR8 and rSC35M. Sera from vaccinated animals activated Fc-gamma receptor IV-mediated effector functions, suggesting that they can induce cell-mediated immune defense mechanisms, such as antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Combination of the most potent antigens NP and M2 in a mixed vaccination resulted in enhanced protection against IAV challenge, suggesting that the antibody responses against these antigens were synergistic. Our results demonstrate the potency of NP and M2 proteins to serve as conserved antigen targets, resulting in broad protection against severe IAV disease.

immunology↗