Lysine acetylation of ribosomal proteins during poliovirus infection limits viral translation

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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.