Ibec Seminar. Monika E. Dolega
Nucleolar mechano-adaptation and its role in epithelial homeostasis
Monika E. Dolega, Institute for Advanced Biosciences IAB, INSERM U1209, CNRS UMR5309, University Grenoble-Alpes, Grenoble, France
Epithelial tissues experience constant mechanical stimuli tied to normal physiological functions, but how they maintain homeostasis under such dynamic conditions remains unclear. Our previous RNAseq study on in-plane compressed epithelial monolayers revealed altered transcripts of ribosomal proteins essential for ribosome biogenesis in nucleoli—membrane-less, sub-nuclear biocondensates that challenge classical mechanotransduction concepts. Although few studies confirm nucleolar sensitivity to external cues, detailed mechanisms are lacking. Using advanced microscopy, omics, and biophysical approaches, we uncover a new mechanism of nucleolar mechano-adaptation. Mechanical confinement over minutes reorganizes nucleolar structure and downregulates pre-rRNA transcription. Central to this process is the nucleolar protein Nucleolin, which translocates to perform two roles: it leaves the rDNA promoter region to down-regulate ribosome biogenesis and participates in DNA repair at damage sites caused by compression. This study introduces the nucleolus as a mechano-sensitive organelle, advancing mechanobiology and cancer research by revealing a new potential therapeutic target
