Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3

Though DNA contains the information needed to build the proteins that keep cells alive, only 2% of the DNA in a human cell codes for proteins. The remaining 98% is referred to as non-coding DNA. The information in some of these non-coding regions can still be copied into molecules of RNA, including long molecules called lncRNAs. Little is known about what lncRNAs actually do, but growing evidence suggests that these molecules are important for a number of vital processes including cell growth and survival. When the DNA in an animal cell gets damaged, the cell needs to decide whether to pause growth and repair the damage, or to kill itself if the harm is too great. One of the best-studied proteins guiding this decision is the p53 protein, which increases the number of protein-coding genes needed to carry out either option in this decision. That is to say that, p53 regulates the genes needed to kill the cell and the genes needed to temporarily pause its growth and repair the damage, which instead keeps the cell alive. So, how does the p53 protein guide the decision, and are lncRNA molecules involved? Using human colon cancer cells, Chaudhary et al. now report that when DNA is damaged, the levels of a specific lncRNA increase 100-fold. Further experiments showed that this lncRNA – named PINCR, which refers to p53-induced noncoding RNA – promotes the survival of cells. Chaudhary et al. showed that PINCR molecules do this by recruiting a protein called Matrin 3 to a certain region in the DNA called an enhancer and then links it to promoter region in the DNA of specific genes that temporarily pause cell growth but keep the cell alive. This in turn activates these ‘pro-survival genes’. In further experiments, when the PINCR molecules were essentially deleted, p53 was not able to fully activate these genes and as a result more of the cells died. Together these findings increase our knowledge of how lncRNAs can work, especially in the context of DNA damage in cancer cells. A next important step will be to uncover other roles for the PINCR molecule in both cancer and healthy cells.