Nonsense mRNA reducing factor-1: Insight into its function through an unpredicted interacting factor

The nonsense-mediated mRNA decay (NMD) pathway serves to reduce the level of mRNAs encoding for premature termination codons. This pathway post-transcriptionally regulates gene expression to down-regulate the production of C terminally truncated proteins. The recognition and subsequent degradation of nonsense mRNA is dependent upon trans-acting factors. These include the Upf1 proteins of Saccharomyces cerevisiae and the SMG proteins of Caenorhabiditis elegans. The mammalian homologue of the Upf1 and SMG-2 proteins, NORF1 (Nonsense mRNA R&barbelow;egulating F&barbelow;actor 1), was initially described by our lab as a structural homologue of Upfl due to the highly conserved cysteine-rich and superfamily I helicase motifs. It has more recently been implicated in mammalian NMD. A dominant-negative form of NORM partially abrogates the rapid decay of nonsense mRNA (Sun et al., 1998). Therefore, we set out to further characterize NORM by investigating its role in NMD and other proteins it interacts with to establish this role. Hence, we identified p32 as a NORM interacting factor. We provide evidence that p32 interacts specifically with NORM, presumably at a location associated with the mitochondria. The yeast p32 homologous protein was not required for NMD; however, we discuss the possible functions of NORM and p32 in regards to their interaction and mitochondria-association.