Identification of Senescence-Associated Circular RNAs (SAC-RNAs) reveals senescence suppressor CircPVT1

With advancing age, senescent cells accumulate in tissues and critically influence aging-associated diseases. We report the first catalog of a novel class of regulatory RNAs, circular RNAs, differentially expressed in senescent (non-dividing) compared with dividing human fibroblasts. Among them, we focused on the circular RNA CircPVT1, as it promoted proliferation by binding and neutralizing let-7, a microRNA capable of triggering senescence. Interestingly, by suppressing let-7, CircPVT1 selectively elevated the expression of several proliferative proteins which were otherwise repressed by let-7. In summary, we have uncovered a novel mechanism whereby circular RNAs control gene expression programs in senescent cells. Overall design: Identification and validation of Senescence-Associated Circular RNAs (SAC-RNAs) in human diploid WI-38 fibroblasts