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

ABSTRACT: Type I interferons (IFN-Is) are essential for antiviral immunity but must be tightly regulated^1-3. The conserved transcriptional repressor SP140 inhibits interferon beta (Ifnb1) expression via an unknown mechanism^4,5. 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 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

SUBMITTER: Witt KC 

PROVIDER: S-EPMC11838211 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature