Nonsense mediated mRNA decay (NMD) is a an mRNA quality control mechanism. This mechanism is highly conserved in eukaryotes being found in organisms as disparate as yeast and humans. The highly conserved nature of this pathway allows us to take advantage of the wide range of tools in S. cerevisiae to examine details of NMD.
A variety of signals on the mRNA can target an mRNA for degradation through this pathway. Known mechanisms for targeting transcripts for NMD decay include improper splicing, premature translation termination, and disabled open reading frames. These mechanisms account for most genes that are susceptible to NMD, however there is a subset of genes with no identifiable NMD targeting features. Recent work indicates some of these genes have a NMD targeting signal in the 3’ untranslated region. My project aims to elucidate the mechanism underlying this novel degradation signal.
Additionally I am examining NMD’s role in adapting cells to environmental stresses. Recent work in S. pombe indicates NMD may assist in adapting to oxidative stress. However, it is unclear if other organisms can use NMD to regulate stress response. I am using S. cerevisiae mutants with an inhibited NMD pathway to screen for stresses that require NMD for rapid adaptation. Our collaboration with the Gasch lab allows us to use microarrays in order to examine how NMD alters the transcriptome to adapt to various stresses.