RNA-binding protein YTHDF3 suppresses interferon-dependent antiviral responses by promoting FOXO3 translation.

ABSTRACT: IFN-stimulated genes (ISGs) are essential effectors of the IFN-dependent antiviral immune response. Dysregulation of ISG expression can cause dysfunctional antiviral responses and autoimmune disorders. Epitranscriptomic regulation, such as N⁶-methyladenosine (m⁶A) modification of mRNAs, plays key roles in diverse biological processes. Here, we found that the m⁶A "reader" YT521-B homology domain-containing family 3 (YTHDF3) suppresses ISG expression under basal conditions by promoting translation of the transcription corepressor forkhead box protein O3 (FOXO3). YTHDF3 cooperates with two cofactors, PABP1 and eIF4G2, to promote FOXO3 translation by binding to the translation initiation region of FOXO3 mRNA. Both the YTH and the P/Q/N-rich domain

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC6338863 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature