Stress granules are shock absorbers that prevent excessive innate immune responses to dsRNA

Proper defense against microbial infection depends on the controlled activation of the immune system. This is particularly important for the RIG-I-like receptors (RLRs), which recognize viral dsRNA and initiate antiviral innate immune responses with the potential of triggering systemic inflammation and immunopathology. Here, we show that stress granules (SGs), molecular condensates that form in response to various stresses including viral dsRNA, play key roles in the controlled activation of RLR signaling. Without the SG nucleators G3BP1/2 and UBAP2L, dsRNA triggers excessive inflammation and immune-mediated apoptosis. In addition to exogenous dsRNA, host-derived dsRNA generated in response to ADAR1 deficiency is also controlled by SG biology. Intriguingly, SGs can function beyond immune control by suppressing viral replication indepen-dently of the RLR pathway. These observations thus highlight the multi-functional nature of SGs as cellular shock absorbersthat converge on protecting cell homeostasis by dampening both toxic immune response and viral replication.

Automated summary

Proper defense against microbial infection relies on controlled activation of the immune system, especially for RIG-I-like receptors (RLRs) recognizing viral dsRNA. Stress granules (SGs) play critical roles in regulating RLR signaling, preventing excessive inflammation and immune-mediated apoptosis. SGs also have the ability to suppress viral replication independently of the RLR pathway, demonstrating their multi-functional nature as cellular shock absorbers for maintaining cell homeostasis.