Coordinated control of senescence by lncRNA UCA1 and a novel CAPERα/TBX3 co-repressor. Homo sapiens

Coordination of a complex series of transcriptional, structural and signaling events culminates in cellular senescence, a crucial tumor suppressor mechanism. We have discovered a repressor complex composed of TBX3 and CAPERa which functions upstream of the RB and p53 effector pathways and is required to prevent senescence of primary cells and in mouse embryos. TBX3/ CAPERa directly binds and represses transcription and chromatin structure of genes in multiple senescence pathways and the LncRNA UCA1, which we have identified as a novel tumor suppressor. The TBX3/ CAPERa complex is physically disrupted in oncogene induced senescence, providing a new molecular mechanism for derepression of prosenescence pathways in this system. Our results provide new insight into the oncogenic properties of TBX3, and are the first demonstration of CAPERa and UCA1 function in vivo. Overall design: mRNA Seq based gene differential expression analysis of two sample types (TBX3, Caper) relative to control and two sample types (pCDNA3.1, UCA1) relative to each other.