The role of TRIM proteins in PRR signaling pathways and immune-related diseases.

Pattern recognition receptors (PRRs) are a kind of recognition molecules mainly expressed on innate immune cells. PRRs recognize one or more kinds of pathogen-associated molecular patterns (PAMPs), inducing the production of interleukin (IL), tumor necrosis factor (TNF), interferon (IFN) and other related cytokines to aggravate immune-related diseases. PPR signaling pathways play an important role in both innate and adaptive immune system, and they are easy to be activated or regulated. Tripartite motif (TRIM) proteins are a group of highly conserved proteins in structure. Most of TRIM proteins contain RING domain, which is thought to play a role in ubiquitination. TRIM proteins are involved in viral immunity, inflammatory response, autophagy, and tumor growth. In this review, we focus on the regulation of TRIM proteins on PRR signaling pathways and their roles in immune-related diseases.

Structural analysis of RIG-I-like receptors reveals ancient rules of engagement between diverse RNA helicases and TRIM ubiquitin ligases.

RNA helicases and E3 ubiquitin ligases mediate many critical functions in cells, but their actions have largely been studied in distinct biological contexts. Here, we uncover evolutionarily conserved rules of engagement between RNA helicases and tripartite motif (TRIM) E3 ligases that lead to their functional coordination in vertebrate innate immunity. Using cryoelectron microscopy and biochemistry, we show that RIG-I-like receptors (RLRs), viral RNA receptors with helicase domains, interact with their cognate TRIM/TRIM-like E3 ligases through similar epitopes in the helicase domains. Their interactions are avidity driven, restricting the actions of TRIM/TRIM-like proteins and consequent immune activation to RLR multimers. Mass spectrometry and phylogeny-guided biochemical analyses further reveal that similar rules of engagement may apply to diverse RNA helicases and TRIM/TRIM-like proteins. Our analyses suggest not only conserved substrates for TRIM proteins but also, unexpectedly, deep evolutionary connections between TRIM proteins and RNA helicases, linking ubiquitin and RNA biology throughout animal evolution.