MYC Drives mRNA Pseudouridylation to Mitigate Proliferation-Induced Cellular Stress during Cancer Development.

ABSTRACT: Pseudouridylation is a common RNA modification that is catalyzed by the family of pseudouridine synthases (PUS). Pseudouridylation can increase RNA stability and rigidity, thereby impacting RNA splicing, processing, and translation. Given that RNA metabolism is frequently altered in cancer, pseudouridylation may be a functionally important process in tumor biology. Here, we show that the MYC family of oncoproteins transcriptionally upregulates PUS7 expression during cancer development. PUS7 is essential for the growth and survival of MYC-driven cancer cells and xenografts by promoting adaptive stress responses and amino acid biosynthesis and import. ATF4, a master regulator of stress responses and cellular metabolism, was identified as a key downstream mediator of PUS7 functional activity.

SUBMITTER: Ding J 

PROVIDER: S-EPMC11609627 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature