Ras-GTPase-activating protein-binding protein 1 (G3BP1) is a core component and crucial regulatory switch in stress granules (SGs). When the concentration of free RNA within cells increases, it can trigger RNA-dependent liquid-liquid phase separation (LLPS) with G3BP1 as the core, thereby forming SGs that affect cell survival or death. In addition, G3BP1 interacts with various host proteins to regulate the expression of SGs. As a multifunctional binding protein, G3BP1 has diverse biological functions, influencing cell proliferation, differentiation, apoptosis, and RNA metabolism and serving as a crucial regulator in signaling pathways such as Rac1-PAK1, TSC-mTORC1, NF-κB, and STAT3. Therefore, it plays a significant role in the regulation of neurodegenerative diseases, myocardial hypertrophy, and congenital immunity, and is involved in the proliferation, invasion, and metastasis of cancer cells. G3BP1 is an important antiviral factor that interacts with viral proteins, and regulates SG assembly to exert antiviral effects. This article focuses on the recent discoveries and progress of G3BP1 in biology, including its structure and function, regulation of SG formation and dissolution, and its relationships with non-neoplastic diseases, tumors, and viruses.
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http://dx.doi.org/10.1016/j.ijbiomac.2024.137254 | DOI Listing |
Mol Cell
December 2024
Biotechnology Center, Center for Molecular and Cellular Bioengineering, TU Dresden, Dresden 01307 Saxony, Germany; Cluster of Excellence Physics of Life, TU Dresden, Dresden 01307 Saxony, Germany. Electronic address:
Ribonucleoprotein (RNP) granules have been linked to translation regulation and disease, but their assembly and regulatory mechanisms are not well understood. Here, we show that the RNA-binding protein G3BP1 preferentially interacts with unfolded RNA, driving the assembly of RNP granule-like condensates that establish RNA-RNA interactions. These RNA-RNA interactions limit the mobility and translatability of sequestered mRNAs and stabilize the condensates.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 2A Nanwei Road, Xicheng District, Beijing 100050, China.
Stress granules (SGs) are membraneless cytoplasmic compartments that form in response to stress stimuli. In these compartments, most translation factors stall, except for activating transcription factor 4 (ATF4), which is preferentially translated to ensure cell survival under stressful conditions. Cancer cells encounter various stress conditions in the tumor microenvironment during tumorigenesis; however, how they exploit the pro-survival effects of ATF4 in SGs remains unclear.
View Article and Find Full Text PDFBiochemistry
December 2024
Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
The Ras GTPase-activating protein SH3-domain-binding protein 1 (G3BP1) serves as a formidable barrier to viral replication by generating stress granules (SGs) in response to viral infections. Interestingly, viruses, including SARS-CoV-2, have evolved defensive mechanisms to hijack SG proteins like G3BP1 for the dissipation of SGs that lead to the evasion of the host's immune responses. Previous research has demonstrated that the interaction between the NTF2-like domain of G3BP1 (G3BP1) and the intrinsically disordered N-terminal domain (NTD-N) of the N-protein plays a crucial role in regulating viral replication and pathogenicity.
View Article and Find Full Text PDFJ Mater Chem B
December 2024
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Biomolecular condensates (BCs) are crucial membraneless organelles formed through the process of liquid-liquid phase separation (LLPS) involving proteins and nucleic acids. These LLPS processes are tightly linked with essential cellular activities. Stress granules (SGs), functioning as cytoplasmic BCs, play indispensable roles in maintaining cellular homeostasis and are implicated in diseases like cancers and neurodegenerative disorders.
View Article and Find Full Text PDFElife
December 2024
Laboratory of Genetics and Genomics, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, United States.
Cells react to stress by triggering response pathways, leading to extensive alterations in the transcriptome to restore cellular homeostasis. The role of RNA metabolism in shaping the cellular response to stress is vital, yet the global changes in RNA stability under these conditions remain unclear. In this work, we employ direct RNA sequencing with nanopores, enhanced by 5' end adapter ligation, to comprehensively interrogate the human transcriptome at single-molecule and -nucleotide resolution.
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