Reciprocal modulation of long noncoding RNA EMS and p53 regulates tumorigenesis

Abstract

Significance As a master transcription factor, the tumor suppressor p53 regulates a variety of cellular processes by modulating target gene expression. Although well known as a transcriptional activator, p53 is also able to repress expression of a number of protein-coding genes. However, it remains largely unknown whether long noncoding RNA (lncRNA) gene repression is involved in the regulation of p53 function. Here, we show that p53 can transcriptionally repress expression of the lncRNA E2F1 messenger RNA (mRNA) stabilizing factor (EMS) and vice versa and that EMS can suppress p53 translation and negatively regulate p53 function. Our study reveals an important double-negative feedback loop that controls p53 activity and provides insights into the mechanisms whereby EMS promotes tumorigenesis.