mRNA transcripts that contain premature termination codons are degraded in a regulated manner by a specific decay pathway termed mRNA surveillance or nonsense mediated mRNA decay (NMD). mRNA surveillance has been described in all eukaryotes tested including plants, flies, yeast, nematodes, and mammals. While much progress has been made in defining the cis-acting elements and trans-acting factors necessary for mRNA surveillance, less is know about the source or features of the mRNA substrates subject to decay. The overall goal of this project is to learn more about the mRNAs produced during the normal course of gene expression that are substrates of mRNA surveillance. In order to systematically investigate these """"""""natural"""""""" targets of NMD, I have probed high density microarrays of cDNA clones from the soil nematode, C. elegans. I intend to use this preliminary data to answer three general questions about the role of mRINA surveillance in """"""""normal"""""""" gene expression: (1) What mRNAs produced during normal gene expression in a wild-type animal serve as """"""""natural"""""""" targets of mRNA surveillance? (2) How are these targets different from those transcripts immune to mRNA surveillance? (3) Do nonsense transcripts arise from errors in transcription, processing, and/or transport? These studies will contribute to our understanding of the molecular mechanisms of mRNA turnover and the biological role of mRNA surveillance.
