Biology subjects

Tournier, C.

Publications and source records attributed to Tournier, C..

2 recordsLinked to original sources

bioRxiv2025

Eukaryotic translation initiation factor 3d regulates stress granule assembly via its RNA binding domain

Stress granules are cytoplasmic mRNA-protein complexes that form by liquid-liquid phase separation in response to a variety of stresses. Their assembly is contingent upon the inhibition of mRNA translation. Depending on the type of stress and severity, they can promote stress resistance or act to reduce cellular fitness. As such, stress granules are implicated in ageing and a range of related pathologies. Many translation factors are components of stress granules, but it is unclear how they contribute to granule assembly. Here we show that the eIF3d component of the eIF3 translation initiation complex is recruited to stress granules in human cells and is required for stress granule assembly in response to specific stresses. The RNA-binding domain of eIF3d mediates its recruitment to stress granules and deletion of this domain blocks granule formation and decreases cell viability. Furthermore, the exogenous expression of just the eIF3d RNA-binding domain can rescue stress granule assembly in eIF3d-depleted cells. We confirmed the importance of eIF3d for robust stress granule assembly in vivo using the nematode worm C. elegans. This study demonstrates that eIF3d is a critical evolutionary conserved stress granule assembly factor, rather than simply coalescing passively into stress granules following the inhibition of translation initiation.

cell biology↗

bioRxiv2021

Mitogen Kinase Kinase (MKK7) controls cytokine production in vitro and in vivo in mice

Mitogen kinase kinase 4 (MKK4) and Mitogen kinase kinase 7 (MKK7) are members of the MAP2K family which can activate downstream mitogen-activated protein kinases (MAPKs). MKK4 has been implicated in the activation of both, c-Jun N-terminal Kinase (JNK) and p38 MAPK, whereas MKK7 only activates JNK in response to different stimuli. The stimuli as well as cell type determine the choice of MAP2K member that mediates the response. In a variety of cell types, the MKK7 contributes to the activation of downstream MAPKs, JNK, which is known to regulate essential cellular processes, such as cell death, differentiation, stress response, and cytokine secretion. Previous studies have implicated the role of MKK7 in stress signaling pathways and cytokine production. However, little is known about the degree to which MKK7 and MKK4 contributes to innate immune response in macrophages as well as during inflammation in vivo. To address this question and elucidate the role of MKK7 and MKK4 in macrophage and in vivo, we developed MKK7- and MKK4-deficient mouse models with tamoxifen-inducible Rosa26 CreERT. This study reports that MKK7 is required for JNK activation both in vitro and in vivo. Additionally, we demonstrated that MKK7 in macrophages is necessary for LPS induced cytokine production and migration which appears to be a major contributor to the inflammatory response in vivo. Whereas MKK4 plays a significant but minor role in cytokine production in vivo.

biochemistry↗