Caveolae Impacts Cellular RNA Levels through Transcription and Translational Processes

Abstract

ABSTRACTCaveolae are membrane domains that provide mechanical strength to cells and localize signaling molecules. Caveolae are composed of caveolin-1 or −3 (Cav1/3) molecules that assemble into domains with the help of cavin-1. Besides organizing caveolae, cavin-1, also known as Polymerase I and Transcript Release Factor (PTRF), promotes ribosomal RNA transcription in the nucleus. Cell expression of Cav1 and cavin-1 are linked. Here, we find that deforming caveolae by subjecting cells to mild osmotic stress (300 to 150 mOsm), changes the levels of cellular proteins (GAPDH, Hsp90 and Ras) change only when Cav1/cavin-1 levels are reduced suggesting link between caveolae deformation and protein expression. We find that this link may be due to relocalization of cavin-1 from the plasma membrane to the nucleus upon caveolae deformation caused by osmotic stress. Cavin-1 relocalization is also seen when Cav1-Gαq contacts change upon stimulation with carbachol. Cav1 and cavin-1 levels have profound effects on the amount of cytosolic RNA and the size distribution of these RNAs that in turn impact the ability of cells to form stress granules and RNA-processing bodies (p-bodies) that protect mRNA when cells are subjected to environmental stress. Studies using a cavin-1 knock-out cell line show adaptive changes in cytosolic RNA levels but a reduced ability to form stress granules. Our studies show that caveolae, through release of cavin-1, communicates mechanical and chemical cues to the cell interior to impact transcriptional and translational processes.