Proteomic screening identifies RPLp2 as a specific regulator for the translation of coronavirus

Dong, Hui-Jun; Wang, Jing; Zhang, Xiuzhong; Li, Cuicui; Liu, Jianfeng; Wang, Xiao-Jia

doi:10.1016/j.ijbiomac.2023.123191

Cited by 5 publications

(3 citation statements)

References 63 publications

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“…RPS28/eS28 and RPLP2 are more abundant than other RPs in the present study. Interestingly, RPS28/eS28 age-downregulated variants have been described in Drosophila, generating a ribosomal heterogeneity that regulates the muscle proteome, while RPLP2 has been described as a translational activator for several viruses, including hepatitis B virus and coronavirus [ 43 , 44 , 45 ]. In contrast, RPS27A/eS31, RPL36A/eL42 and RPL37/eL37 are substoichiometric in our data.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Ribosomal Protein MRPS15 Is a Component of Cytosolic Ribosomes and Regulates Translation in Stressed Cardiomyocytes

David,

Roussel,

Froment

et al. 2024

IJMS

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Regulation of mRNA translation is a crucial step in controlling gene expression in stressed cells, impacting many pathologies, including heart ischemia. In recent years, ribosome heterogeneity has emerged as a key control mechanism driving the translation of subsets of mRNAs. In this study, we investigated variations in ribosome composition in human cardiomyocytes subjected to endoplasmic reticulum stress induced by tunicamycin treatment. Our findings demonstrate that this stress inhibits global translation in cardiomyocytes while activating internal ribosome entry site (IRES)-dependent translation. Analysis of translating ribosome composition in stressed and unstressed cardiomyocytes was conducted using mass spectrometry. We observed no significant changes in ribosomal protein composition, but several mitochondrial ribosomal proteins (MRPs) were identified in cytosolic polysomes, showing drastic variations between stressed and unstressed cells. The most notable increase in polysomes of stressed cells was observed in MRPS15. Its interaction with ribosomal proteins was confirmed by proximity ligation assay (PLA) and immunoprecipitation, suggesting its intrinsic role as a ribosomal component during stress. Knock-down or overexpression experiments of MRPS15 revealed its role as an activator of IRES-dependent translation. Furthermore, polysome profiling after immunoprecipitation with anti-MRPS15 antibody revealed that the “MRPS15 ribosome” is specialized in translating mRNAs involved in the unfolded protein response.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial Ribosomal Protein MRPS15 Is a Component of Cytosolic Ribosomes and Regulates Translation in Stressed Cardiomyocytes

David,

Roussel,

Froment

et al. 2024

IJMS

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“…Similar to eukaryotic translation regulation, the CoV mRNA 5′ cap binds eIF4E to control eIF4F complex formation and interferes with cellular translation via phosphorylation on serine 209 [ 66 ]. Similarly, the regulatory role of p-eIF4E in HSV translation was reported in the early 2000s [ 67 ].…”

Section: Natural Products Targeting Viral Translationmentioning

confidence: 99%

“…In subsequent experiments, we found that p-eIF4E was involved in regulating some cytokines that affect PEDV replication. Therefore, we believe that p-eIF4E is a potential antiviral target [ 66 ].…”

Section: Natural Products Targeting Viral Translationmentioning

confidence: 99%

Broad-Spectrum Antivirals Derived from Natural Products

Tian

Wang

2023

Viruses

Self Cite

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Scientific advances have led to the development and production of numerous vaccines and antiviral drugs, but viruses, including re-emerging and emerging viruses, such as SARS-CoV-2, remain a major threat to human health. Many antiviral agents are rarely used in clinical treatment, however, because of their inefficacy and resistance. The toxicity of natural products may be lower, and some natural products have multiple targets, which means less resistance. Therefore, natural products may be an effective means to solve virus infection in the future. New techniques and ideas are currently being developed for the design and screening of antiviral drugs thanks to recent revelations about virus replication mechanisms and the advancement of molecular docking technology. This review will summarize recently discovered antiviral drugs, mechanisms of action, and screening and design strategies for novel antiviral agents.

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Cellular RNA-binding proteins LARP4 and PABPC1 synergistically facilitate viral translation of coronavirus PEDV

Wang,

Zhang,

Sun

et al. 2024

Veterinary Microbiology

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Proteomic screening identifies RPLp2 as a specific regulator for the translation of coronavirus

Cited by 5 publications

References 63 publications

Mitochondrial Ribosomal Protein MRPS15 Is a Component of Cytosolic Ribosomes and Regulates Translation in Stressed Cardiomyocytes

Mitochondrial Ribosomal Protein MRPS15 Is a Component of Cytosolic Ribosomes and Regulates Translation in Stressed Cardiomyocytes

Broad-Spectrum Antivirals Derived from Natural Products

Cellular RNA-binding proteins LARP4 and PABPC1 synergistically facilitate viral translation of coronavirus PEDV

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