Rmi1 connects genomic instability with transcriptional noise through Xist.

We studied the transcriptional properties of Rmi1, a molecule associated with genomic instability. Rmi1 was widely expressed in human cancer. Co-regulation of Rmi1 with Rb1 suggested Rmi1 was connected to tumor suppression. Accordingly, Rmi1 was activated in intraepithelial neoplasia in humans in vivo. Rmi1 was expressed in a p53 status dependent fashion in the tumors of humans with lung cancer. Rmi1 could be controlled by transgenic expression of Xist, and was co-regulated with components of the Xist RNP, including KHDRBS1 and ILF2. Rmi1 co-regulation with DNMT1, PARP1 and TET2 indicated Rmi1 function was associated with repair and methylation of the DNA. The function of Rmi1 in genomic instability, the fact that Rmi1 is a marker of genomic instability, Rmi1 co-regulation with tumor suppression, activation of Rmi1 in transformation and human cancer, and control of Rmi by Xist is indicative of a function for Xist and the imprinting system in establishing homeostatic transcriptional control through regulation or balancing of “transcriptional noise” which becomes dysregulated in cancer.