c-MYC mRNA tail tale about glutamine control of transcription

Abstract

Dejure et al (2017) demonstrates an intriguing link between glutamine, c‐MYC protein levels, and c‐MYC‐dependent transcription. Glutamine‐dependent c‐MYC protein level, which is sensed through the c‐MYC mRNA 3′‐UTR, determines global transcriptional response to glutamine deprivation in HCT116 colon cancer cells. These findings add another layer of complexity to c‐MYC's role as a nexus in metabolic regulation.

Figure 1. Glutamine‐dependent MYC‐mediated transcription

The diagram illustrates the finding by Dejure et al (2017) that glutamine contributes to adenosine synthesis, which in turn promotes c‐MYC mRNA translation via the 3′‐UTR. However, as depicted, whether adenosine signals directly or indirectly to the 3′‐UTR via a protein, such as HuR remains to be established. HuR has been documented to affect c‐MYC mRNA level and translation. Further, whether adenosine plays a role in signaling via an adenosine receptor or is involved in RNA editing (through adenosine deaminase acting on RNA or ADAR) or synthesis requires additional studies. Although glutamine does not seem to affect c‐MYC protein stability in HCT116 cells, it has been shown to affect O‐linked glycosylation and stability of c‐MYC protein. The diagram also illustrates that c‐MYC levels are regulated by a number of factors that affect transcription through RNA polymerase II (Pol II) pause‐release.