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.

Public Health Relevance

Ribosomes, the key molecules of cellular protein production, contain modified ribosomal proteins but the exact functions of these ribosome modifications are currently unknown. Because we find that ribosome acetylations are altered during poliovirus infection and appear to have antiviral function we propose to identify the enzyme acetylating ribosomal proteins, the exact ribosomal protein targets and the impact these enzymes have on poliovirus translation. This initial study will enable us to investigate the function of ribosome acetylation during viral infection in greater detail in the future.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
1R03AI144839-01A1
Application #
9896367
Study Section
Virology - A Study Section (VIRA)
Program Officer
Park, Eun-Chung
Project Start
2020-02-01
Project End
2022-01-31
Budget Start
2020-02-01
Budget End
2021-01-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
State University of New York at Albany
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
152652822
City
Albany
State
NY
Country
United States
Zip Code
12222