SP140-RESIST pathway regulates interferon mRNA stability and antiviral immunity.

ABSTRACT: Type I interferons are essential for antiviral immunity¹ but must be tightly regulated². The conserved transcriptional repressor SP140 inhibits interferon-β (Ifnb1) expression through an unknown mechanism^3,4. Here we report that SP140 does not directly repress Ifnb1 transcription. Instead, SP140 negatively regulates Ifnb1 mRNA stability by directly repressing the expression of a previously uncharacterized regulator that we call RESIST (regulated stimulator of interferon via stabilization of transcript; previously annotated as annexin 2 receptor). RESIST promotes Ifnb1 mRNA stability by counteracting Ifnb1 mRNA destabilization mediated by the tristetraprolin (TTP) family of RNA-binding proteins and the CCR4-NOT deadenylase complex. SP140 localizes within pun

SUBMITTER: Witt KC 

PROVIDER: S-EPMC12310523 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature