UBAP2L arginine methylation by PRMT1 modulates stress granule assembly

Chuyu Huang,Yan Chen,Minyu Xie,Zhenguo Chen,Xiaochun Bai,Feilong Chen,Xiangjin Kang,Hanbin Zhang,Huaiqian Dai,Huan Zhang

doi:10.1038/s41418-019-0350-5

Abstract

Stress granules (SGs) are discrete assemblies of stalled messenger ribonucleoprotein complexes (mRNPs) that form when eukaryotic cells encounter environmental stress. RNA-binding proteins (RBPs) mediate their condensation by recruiting populations of mRNPs. However, the cellular and molecular mechanisms underlying the role of ubiquitin-associated protein 2-like (UBAP2L) in the regulation of SG dynamics remain elusive. Here, we show that UBAP2L is required for both SG assembly and disassembly. UBAP2L overexpression nucleated SGs under stress-null conditions. The UBAP2L Arg–Gly–Gly (RGG) motif was required for SG competence, and mediated the recruitment of SG components, including mRNPs, RBPs, and ribosomal subunits. The domain of unknown function (DUF) of UBAP2L-mediated interaction with ras GTPase-activating protein-binding protein (G3BP)1/2, and its deletion caused the cytoplasmic–nuclear transport of UBAP2L and G3BP1/2, thereby compromising SG formation. The protein arginine methyltransferase PRMT1 asymmetrically dimethylated UBAP2L by targeting the RGG motif. Increased arginine methylation blocked, whereas its decrease enhanced UBAP2L interactions with SG components, ablating and promoting SG assembly, respectively. These results provide new insights into the mechanisms by which UBAP2L regulates SG dynamics and RNA metabolism.

Highlights

Stress granules (SGs) are cytoplasmic foci that are assembled when untranslated messenger ribonucleoprotein complexes accumulate in eukaryotic cells exposed to biotic stress or environmental stressThese authors contributed : Chuyu Huang, Yan ChenEdited by D
These results suggest that the recruited SG components through its Arg–Gly–Gly (RGG) motif is universally required for ubiquitin-associated protein 2-like (UBAP2L)-mediated SG formation by recruiting other nucleators and ribosomal subunits, and the domain of unknown function (DUF) domain mediates the molecular interactions between UBAP2L and G3BP, which synergistically contribute to SG nucleation
No significant change in SG formation was observed under normal or AS-stressed condition (Fig. 5h and i), and the PRMT1 association and asymmetric dimethylarginine (ADMA) signal were still detected (Fig. 5j). These data demonstrated that the RGG motif in UBAP2L was asymmetrically dimethylated by PRMT1

Summary

Introduction

Stress granules (SGs) are cytoplasmic foci that are assembled when untranslated messenger ribonucleoprotein complexes (mRNPs) accumulate in eukaryotic cells exposed to biotic stress (e.g., viral infections) or environmental stress. Ubiquitin-associated protein 2-like (UBAP2L) is a highly conserved protein with an N-terminal ubiquitinassociated (UBA) domain involved in the ubiquitin– proteasome system and aggregate formation induced by proteasome inhibitors [22]. It was originally identified as a human sperm protein that interacts with zona pellucida 3 in human eggs [23]. A recent study suggested that it is involved in SG formation [32]; the cellular and molecular mechanisms underlying the role of UBAP2L in the regulation of SG assembly and disassembly need to be further investigated. We propose a model to explain the function of UBAP2L in SG condensation

Materials and methods

Results

Discussion

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