# Sec8: a novel positive regulator of RIG-I in anti-RNA viral defense

## TL;DR

This paper shows that Sec8 helps the immune system fight RNA viruses by supporting RIG-I, a key protein in antiviral defense.

## Contribution

Sec8 is newly identified as a positive regulator of RIG-I, stabilizing it to enhance antiviral innate immune responses.

## Key findings

- Sec8 stabilizes RIG-I by inhibiting its ubiquitination and proteasome-mediated degradation.
- Sec8 suppresses STUB1 activity by reducing p53 expression and competing for RIG-I binding.
- Mice lacking Sec8 are more susceptible to RNA virus infections.

## Abstract

Sec8, an exocyst complex subunit, is pivotal in facilitating the docking of exocytic vesicles to fusion sites on the plasma membrane. However, its involvement in the antiviral innate immune response and virus replication remains unclear. In this study, Sec8 is identified as a novel positive regulator of RIG-I, enhancing the IFN-I signaling response against RNA viruses both in vivo and in vitro. Additionally, Sec8 stabilizes RIG-I by inhibiting its ubiquitination and subsequent proteasome-mediated degradation. Mechanistically, STUB1 degrades RIG-I via K48-linked ubiquitination at Lys190, while Sec8 suppresses STUB1 mRNA by reducing the expression of p53 and competes with STUB1 for binding to RIG-I’s CARD domain, thereby preventing STUB1-mediated RIG-I degradation. Importantly, Sec8-deficient mice were more susceptible to RNA virus infection compared to wild-type mice. These findings elucidate a mechanism that Sec8 positively regulates RIG-I in the antiviral innate immune response, offering insights for developing novel therapeutic strategies and targeted antiviral medications.