Analysis of the physiological roles of the nonsense mediated MRNA decay pathway in Drosophila Melanogaster

The nonsense mediated mRNA decay (NMD) pathway is a conserved posttranscriptional mRNA decay pathway that functions to destabilize a variety of naturally occurring target mRNAs. The NMD pathway functions in all eukaryotes and regulates a significant portion of the transcriptome. It is thought that this regulation is critical as inhibition of NMD leads to physiological and developmental defects in all organisms and in the case of more complex organisms, lethality. It is predicted that overexpression of NMD pathway target genes leads to these defects in NMD mutants. Despite the critical nature of this pathway, little is know about how NMD functions in a developmental and physiological context, including which target genes are most critically regulated by NMD and how the overexpression of these targets may mediate the NMD mutant phenotype. To address this knowledge gap, we first use two genome-wide techniques to identify and characterize the kinds of transcripts targeted by NMD in the context of an intact metazoan, Drosophila melanogaster. We then examine more closely the function of one of these target genes, Gadd45, and find that overexpression of this target in NMD mutants may explain important aspects of the NMD mutant phenotype.