YAMAMOTO, K. | Search bioRxiv

bioRxiv2026

Identification of the Down syndrome critical region 3 gene as a mammalian cell size regulator

Using a genetic screening approach based on an inducible gene-activating system and cell sorting, Down syndrome critical region 3 (DSCR3) was isolated as a gene whose overexpression increased cell size. Fibroblasts derived from individuals with Down syndrome (DS) exhibit elevated DSCR3 expression at both the mRNA and protein levels, correlating with increased cell volume compared to fibroblasts from healthy donors. Despite a slower proliferation rate, DS fibroblasts demonstrate higher basal and maximal mitochondrial respiration, suggesting enhanced metabolic activity associated with increased cell size. siRNA-mediated knockdown of DSCR3 reduces cell size in both DS and normal fibroblasts, indicating its general role in cell size regulation. As DSCR3 is a component of the retriever complex involved in endosomal cargo recycling, these findings position membrane protein trafficking as a novel module for cell size control.

cell biology↗

bioRxiv2026

Structural Basis of H-NS-Mediated Temperature-Dependent Stimulation of Initial Growth in Escherichia coli.

Bacteria have evolved sophisticated mechanisms to sense and adapt to environmental shifts, particularly when transitioning into the stable, warm temperatures of a host organism. Escherichia coli, a primary inhabitant of the warm-blooded host gut, must rapidly initiate growth upon entry to ensure reproductive success. In this study, we demonstrate that the specific growth rate at the onset of the logarithmic phase (defined as at ODratio=0.2) is specifically stimulated across a medium temperature range (30{degrees}C-42{degrees}C), peaking near the physiological temperature of 37{degrees}C. This adaptive response is strain-specific and depends on both the histone-like nucleoid-associated protein (NAP) H-NS and the presence of the Rac prophage. Using high-frequency automated growth monitoring and statistical modeling, we redefine H-NS not merely as a gene silencer but as a critical "nucleoid structural organizer". Our results indicate that H-NS undergoes a conformational switch at approximately 37{degrees}C, transitioning into a parallel form that provides the necessary physical scaffold for nucleoid reorganization. This reorganization is essential for coordinating transcription and replication during the rapid onset of growth. Crucially, we resolve the "silencing paradox": while H-NS silencing is traditionally thought to be weakened at 37{degrees}C, hns-deficient mutants grow significantly slower because they lack this essential structural scaffold. We conclude that the H-NS-mediated physical organization of the genome is more critical for host adaptation than the mere de-repression of the genomic reservoir, enabling E. coli to effectively transition into a high-growth state for successful host colonization.

microbiology↗