Juvenility-associated lncRNA Gm14230 maintains cellular juvenescence

Juvenile animals possess distinct properties that are missing in adults. These properties include capabilities for higher growth, faster wound healing, plasticity and regeneration. However, the molecular mechanisms underlying these juvenile physiological properties are not fully understood. To obtain insight into the distinctiveness of juveniles from adults at the molecular level, we assessed long noncoding RNAs (lncRNAs) that are highly expressed selectively in juvenile cells. The noncoding elements of the transcriptome were investigated in hepatocytes and cardiomyocytes isolated from juvenile and adult mice. Here, we identified 62 juvenility-associated lncRNAs (JAlncs) which are selectively expressed in both hepatocytes and cardiomyocytes from juvenile mice. Among these common JAlncs, Gm14230 is evolutionarily conserved and is essential for cellular juvenescence. Loss of Gm14230 impairs cell growth and causes cellular senescence. Gm14230 safeguards cellular juvenescence through recruiting Ezh2 histone methyltransferase to Tgif2, thereby repressing Tgfi2 functional role in cellular senescence. Thus, we disclose Gm14230 as a juvenility-selective lncRNA required to maintain cellular juvenescence.