A central tenet of biology is the accurate flow of information from nucleic acids to proteins through the genetic code. It is commonly believed that translation deviating from the genetic code is to be avoided at all times in cells. By using a new genomic method, we have discovered that in contrary, mammalian cells can deliberately reprogram the genetic code with the amino acid methionine upon innate immune activation and chemically triggered oxidative stress. Reprogramming the genetic code occurs through aminoacylation of non-methionyl-tRNAs with methionine, and is inducible upon regulated production of the reactive oxygen species (ROS) in the cell. We propose that mis-translation via regulated tRNA misacylation is a common mechanism for stress response for cells. We will explore and test hypotheses on biological effects and function on tRNA misacylation with methionine and establish a full spectrum of tRNA misacylation for all amino acids and their participations in translation in mammalian cells. The results and conceptual understanding obtained here shall help establish a new field of biology of mis-translation.

Public Health Relevance

We have discovered that mammalian cells deliberately reprogram the genetic code with the amino acid methionine upon innate immune activation and oxidative stress. Here we aim to establish biology of mis-translation via tRNA misacylation as a new mechanism of stress response in mammalian cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
5DP1GM105386-04
Application #
8710281
Study Section
Special Emphasis Panel (ZGM1-NDPA-A (01))
Program Officer
Bender, Michael T
Project Start
2011-09-30
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
4
Fiscal Year
2014
Total Cost
$780,000
Indirect Cost
$280,000
Name
University of Chicago
Department
Biochemistry
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637