ABSTRACT
Stress granules (SGs) are membrane-less organelles (MLOs) or cytosolic compartments formed upon exposure to environmental cell stress-inducing stimuli. SGs are based on ribonucleoprotein complexes from a set of cytoplasmic proteins and mRNAs, blocked in translation due to stress cell-induced polysome disassembly. Post-translational modifications (PTMs) such as methylation, are involved in SG assembly, with the methylation writer PRMT1 and its reader TDRD3 colocalizing to SGs. However, the role of this writer-reader system in SG assembly remains unclear. Here, we found that PRMT1 methylates SG constituent RNA-binding proteins (RBPs) on their RGG motifs. Besides, we report that TDRD3, as a reader of asymmetric dimethylarginines, enhances RNA binding to recruit additional RNAs and RBPs, lowering the percolation threshold and promoting SG assembly. Our study enriches our understanding of the molecular mechanism of SG formation by elucidating the functions of PRMT1 and TDRD3. We anticipate that our study will provide a new perspective for comprehensively understanding the functions of PTMs in liquid-liquid phase separation driven condensate assembly.
Subject(s)
Protein-Arginine N-Methyltransferases , RNA-Binding Proteins , Stress Granules , Humans , Methylation , Protein Binding , Protein Interaction Maps , Protein Processing, Post-Translational , Protein-Arginine N-Methyltransferases/metabolism , Protein-Arginine N-Methyltransferases/genetics , Repressor Proteins/metabolism , Repressor Proteins/genetics , RNA-Binding Proteins/metabolism , Stress Granules/metabolismABSTRACT
Stress granules (SGs) are dynamic biomolecular condensates that form in the cytoplasm in response to cellular stress, encapsulating proteins and RNAs. Methylation is a key factor in the assembly of SGs, with PRMT1, which acts as an arginine methyltransferase, localizing to SGs. However, the precise mechanism of PRMT1 localization within SGs remains unknown. In this study, we identified that Caprin1 plays a primary role in the recruitment of PRMT1 to SGs, particularly through its C-terminal domain. Our findings demonstrate that Caprin1 serves a dual function as both a linker, facilitating the formation of a PRMT1-G3BP1 complex, and as a spacer, preventing the aberrant formation of SGs under non-stress conditions. This study sheds new lights on the regulatory mechanisms governing SG formation and suggests that Caprin1 plays a critical role in cellular responses to stress.