TY - JOUR T1 - Stress granules are shock absorbers that prevent excessive innate immune responses to dsRNA JF - bioRxiv DO - 10.1101/2021.04.26.441141 SP - 2021.04.26.441141 AU - Max Paget AU - Cristhian Cadena AU - Sadeem Ahmad AU - Hai-Tao Wang AU - Tristan X. Jordan AU - Ehyun Kim AU - Beechui Koo AU - Shawn M. Lyons AU - Pavel Ivanov AU - Benjamin tenOever AU - Xin Mu AU - Sun Hur Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/07/20/2021.04.26.441141.abstract N2 - 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 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, we find that 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 independent of the RLR pathway. These observations thus highlight the multi-functional nature of SGs as cellular “shock absorbers” that converge on protecting cell homeostasis–by dampening both toxic immune response and viral replication.Competing Interest StatementThe authors have declared no competing interest. ER -