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Lysine acetylation of ribosomal proteins during poliovirus infection limits viral translation

脊髓灰质炎病毒感染期间核糖体蛋白的赖氨酸乙酰化限制了病毒翻译

基本信息

批准号：
10092928
负责人：
Gabriele Fuchs
金额：
$ 7.73万
依托单位：
STATE UNIVERSITY OF NEW YORK AT ALBANY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10092928
关键词：
Acetylation Acetyltransferase Affect Antiviral Agents Arginine Attention Biological Biological Models Cells Chemicals Common Cold Complementary DNA Coxsackie Viruses Data Defense Mechanisms EP300 gene Enterovirus Enzymes Family Picornaviridae Fireflies Flaviviridae Foundations Future Genetic Translation Genome Goals Grant Hand, Foot and Mouth Disease Hela Cells Hepatitis C virus Human poliovirus Hybrids Immunoblotting In Vitro Infection Investigation Luciferases Lysine Mass Spectrum Analysis Measures Methylation Modification Mutagenesis Oryctolagus cuniculus Peptide Initiation Factors Play Post-Translational Protein Processing Production Protein Acetylation Protein Biosynthesis Proteins RNA Interference RNA Viruses Reporter Research Project Grants Reticulocytes Rhinovirus Ribosomal Proteins Ribosomal RNA Ribosomes Role Small Interfering RNA Stress System Testing Translating Translations Viral Viral Proteins Virus Virus Diseases West Nile virus Zika Virus acute flaccid myelitis biological adaptation to stress machine translation member non-histone protein overexpression prevent stressor translation assay viral RNA

项目摘要

Ribosomal proteins contain numerous posttranslational modifications, but the functions these ribosome modifications play during mRNA translation are currently unknown. Our long-term goal is to study the function of these posttranslational modifications, specifically how they regulate protein biosynthesis. We have found that ribosomal protein acetylations are altered during infection with poliovirus. Mutagenesis of some acetylated lysine residues in eS25, a protein required for poliovirus translation, benefits the virus, suggesting that some acetylations might have antiviral function. The objective of this grant is to identify the acetyltransferase, which modifies ribosomal proteins during poliovirus infection. The central hypothesis is that the same enzyme might target multiple ribosomal proteins, thus, we expect that overexpression or depletion of the acetyltransferase may have a cumulative and pronounced effect on poliovirus translation. Our specific aim will test our central hypothesis by depleting or overexpressing different acetyltransferases and determining the effect on poliovirus translation and ribosome modifications by immunoblotting and mass spectrometry analysis. Our proposal describes a significant paradigm shift from ribosomes as non-discriminatory translation machines, defenseless to viral takeover, to active regulators of protein biosynthesis with antiviral function to protect cells.

核糖体蛋白含有许多翻译后修饰，但这些核糖体修饰在mRNA翻译过程中发挥的功能目前尚不清楚。我们的长期目标是研究这些翻译后修饰的功能，特别是它们如何调节蛋白质的生物合成。我们已经发现核糖体蛋白乙酰化在脊髓灰质炎病毒感染期间发生改变。脊髓灰质炎病毒翻译所需的蛋白质eS25中的一些乙酰化赖氨酸残基的突变对病毒有益，这表明一些乙酰化可能具有抗病毒功能。这项资助的目的是确定乙酰转移酶，它在脊髓灰质炎病毒感染期间修饰核糖体蛋白。中心假设是同一种酶可能靶向多种核糖体蛋白，因此，我们预计乙酰转移酶的过度表达或耗竭可能对脊髓灰质炎病毒翻译产生累积和显著影响。我们的具体目标是通过耗尽或过表达不同的乙酰转移酶并通过免疫印迹和质谱分析确定对脊髓灰质炎病毒翻译和核糖体修饰的影响来测试我们的中心假设。我们的建议描述了一个重要的范式转变，从核糖体作为非歧视性的翻译机器，对病毒接管毫无防备，到具有抗病毒功能的蛋白质生物合成的主动调节剂，以保护细胞。