Biology subjects

Otikovs, L.

Publications and source records attributed to Otikovs, L..

3 recordsLinked to original sources

bioRxiv2026

RTTN moonlights beyond the centrosome to control ribosome biogenesis and tRNA modification in human brain organoids

RTTN (rotatin) is a centrosomal protein mutated in severe malformations of cortical development, yet how its dysfunction disrupts human corticogenesis has remained unclear. Here, we show that RTTN has an unrecognized function at the core of the translation machinery. Using human telencephalic and hippocampal organoids carrying distinct RTTN alleles, together with single-cell and bulk transcriptomics, polysome profiling, and tRNA pseudouridine sequencing, we find that RTTN is enriched in cycling first-trimester neural progenitors and physically associates with ribosome-biogenesis and RNA-processing factors. RTTN mutations impair rRNA biogenesis and polysome assembly, reduce cytoplasmic ribosome density and nascent protein synthesis, and remodel the tRNA pseudouridylation landscape through both a PUS7L-dependent variable-arm signature and a broader RTTN-specific defect. These translational deficits are accompanied by prolonged mitosis, reduced entry into S-phase, and impaired interkinetic nuclear migration in mutant progenitors. Our findings redefine RTTN as a regulator of ribosome homeostasis and mRNA translation and implicate defective translational capacity as a driver of RTTN-associated microcephaly. Graphical AbstractRTTN sustains ribosome and tRNA homeostasis in human neural progenitors; its mutation disrupts mRNA translation, stalling progenitor proliferation and interkinetic nuclear migration, and driving cortical malformation and growth failure. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/744412v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@16124aaorg.highwire.dtl.DTLVardef@ae23f7org.highwire.dtl.DTLVardef@bb588forg.highwire.dtl.DTLVardef@1b35028_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

TLR2-mediated microbial sensing by intestinal stem cells coordinates epithelial antimicrobial defense.

Intestinal regeneration and host defense require adaptation to environmental cues, but the mechanisms underlying this coordination remain unclear. We show that intestinal Lgr5 stem cells act as luminal sensors via apically localized Toll-like receptor 2 (TLR2), enabling direct detection of microbiota-derived signals. We identify apical TLR2 activation as a mechanism of luminal sensing in adult stem cells and show that it controls epithelial differentiation, antimicrobial peptide production, and crypt organization, with a particularly strong influence on Paneth cell maturation. Genetic ablation of constitutive, epithelial, or stem cell-specific TLR2 disrupts these processes, leading to impaired antimicrobial defense and altered epithelial composition. Using germ-free mice and human intestinal organoids, we demonstrate that this pathway is microbiota-dependent and evolutionarily conserved, respectively. These findings support a model in which stem cells act as active integrators of environmental information and suggest a broader principle by which barrier tissues couple microbial sensing to regeneration and host protection.

immunology↗

bioRxiv2026

Intracellular carbon storage enables starvation survival in marine bacteria

Heterotrophic marine bacteria frequently experience fluctuations in carbon availability driven by phytoplankton dynamics. As a result, bacteria undergo repeated cycles of rapid growth during brief resource pulses followed by prolonged starvation. Yet the mechanisms that support bacterial survival during nutrient limitation remain poorly understood. Here, we investigate starvation survival in the algal-associated bacterium Phaeobacter inhibens. We show that cells remain viable for extended periods under carbon depletion while undergoing physiological and morphological changes. Using electron microscopy, metabolomics, and genetic approaches, we identify intracellular polyhydroxybutyrate (PHB) granules as a key factor supporting survival during starvation. PHB accumulates during growth and is progressively consumed under carbon limitation. Deletion of the PHB synthase gene (phaC) eliminates granule formation and reduces long-term viability. Comparative analyses show that the genetic capacity for PHB biosynthesis is widespread among members of the Roseobacter group, suggesting a conserved strategy among algal-associated bacteria. However, species lacking PHB also survive starvation, indicating that additional mechanisms contribute to persistence under nutrient limitation. Together, our results identify intracellular carbon storage as a central mechanism linking bacterial physiology to survival in fluctuating marine environments, and highlight the diversity of strategies shaping microbial community dynamics and carbon cycling in the ocean.

microbiology↗