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Abstract
Viral infection activates transcription factors NF-kappaB and IRF3, which collaborate
to induce type I interferons (IFNs) and elicit innate antiviral response. MITA (also
known as STING) has recently been identified as an adaptor that links virus-sensing
receptors to IRF3 activation. Here, we showed that the E3 ubiquitin ligase RNF5 interacted
with MITA in a viral-infection-dependent manner. Overexpression of RNF5 inhibited
virus-triggered IRF3 activation, IFNB1 expression, and cellular antiviral response,
whereas knockdown of RNF5 had opposite effects. RNF5 targeted MITA at Lys150 for ubiquitination
and degradation after viral infection. Both MITA and RNF5 were located at the mitochondria
and endoplasmic reticulum (ER) and viral infection caused their redistribution to
the ER and mitochondria, respectively. We further found that virus-induced ubiquitination
and degradation of MITA by RNF5 occurred at the mitochondria. These findings suggest
that RNF5 negatively regulates virus-triggered signaling by targeting MITA for ubiquitination
and degradation at the mitochondria.