MYC promotes cancer progression by modulating m⁶ A modifications to suppress target gene translation.

ABSTRACT: The MYC oncoprotein activates and represses gene expression in a transcription-dependent or transcription-independent manner. Modification of mRNA emerges as a key gene expression regulatory nexus. We sought to determine whether MYC alters mRNA modifications and report here that MYC promotes cancer progression by down-regulating N6-methyladenosine (m⁶ A) preferentially in transcripts of a subset of MYC-repressed genes (MRGs). We find that MYC activates the expression of ALKBH5 and reduces m⁶ A levels in the mRNA of the selected MRGs SPI1 and PHF12. We also show that MYC-regulated m⁶ A controls the translation of MRG mRNA via the specific m⁶ A reader YTHDF3. Finally, we find that inhibition of ALKBH5, or overexpression of SPI1 or PHF12, effectivel

SUBMITTER: Wu G 

PROVIDER: S-EPMC7926262 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature