PTC Recognition in Human Nonsense-Mediated mRNA Decay

University Of California-San Diego, La Jolla CA

Investigators

Abstract

The information that controls the growth and function of cells in our body is contained within the genes of our chromosomes. Most genes direct the production of messenger RNAs (mRNAs) by the process of transcription. mRNAs in turn serve as templates for translation into proteins. However, before mRNAs are translated into proteins they need to undergo several processing events, including the removal of non-coding segments called introns by the process of splicing. Sometimes when mRNAs are processed, mistakes happen that cause the mRNAs to encode aberrantly shortened protein products. This can be deleterious to cells, as even small amounts of shortened protein products can in some cases block the process in which the full-length protein normally functions. However, eukaryotic cells have evolved a machinery to identify and degrade such aberrant mRNAs, thus preventing the production of deleterious shortened protein products. This machinery is called the nonsense-mediated mRNA decay pathway, or for short, NMD. NMD is also important for preventing the translation into protein of so-called pseudogenes, which are genes that used to encode proteins, but during evolution have been mutated and become inactivated. The mechanism by which the NMD pathway identifies aberrant mRNAs from those that are normal is mysterious and highly debated. In this project, it will be studied how normal mRNAs have evolved to evade degradation by the NMD machinery, and how the NMD machinery cooperates with the translation process to identify and degrade aberrant mRNAs. This project will train a female graduate student and a postdoctoral researcher, as well as one or more undergraduate students in state-of-the-art molecular biology research. The project is an integral part of the principal investigator's undergraduate and graduate teaching in Molecular Biology at the University of California San Diego, for which new interactive teaching methods will be developed to help convey to college students the importance of the scientific method for both scientific research and for our society.