Research Interests

Our research focuses on understanding the molecular mechanism of mRNA decay. mRNA decay is an important mechanism for regulating gene expression in most if not all organisms, including humans. We are interested in understanding how specialized mRNA decay pathways recognize and target their substrate mRNAs for decay. We are using the nonsense-mediated mRNA decay (NMD) pathway of the yeast Saccharomyces cerevisiae as a model.

Two classes of mRNAs are affected by the NMD pathway. The first class is mRNAs that contain premature termination codons. These mRNAs arise either by transcription of genes containing nonsense or frameshift mutations, or by errors in transcription or processing. The second class is wild-type mRNAs. Approximately 250 of the 6,250 yeast mRNAs accumulate when NMD is inactivated. These mRNAs are either wild-type NMD targets or mRNAs whose abundance increases as an indirect consequence of NMD.

Two current challenges are to understand how some wild-type mRNAs become NMD substrates and sort the NMD-affected mRNAs into direct and indirect targets. We are investigating how wild-type PPR1 mRNA is degraded by NMD and developing a bioinformatics-based approach to address these challenges.

Our studies have broad significance. An understanding of NMD will provide a working model of the decay of mRNAs by specialized pathways. This, in turn, will bring us closer to understanding gene expression and regulation. Amazingly, NMD has been conserved from bacteria to humans, and implicated in the maintenance of epigenetic silencing. Thus, our studies will also contribute to our knowledge of an important mRNA decay pathway.

Recent Publications

• Mosel, D.D., R. Dumitru, J. M. Hornby, A. L. Atkin, and K. W. Nickerson, 2005. Farnesol concentrations required to block germ tube formation in Candida albicans in the presence and absence of serum. Applied and Environmental Microbiology, in press.
• Nazarenus, T., R. Cedarberg, R. Bell, J. Cheatle, A. Forch, A. Haifley, A. Hou, B. W. Kebaara, C. Shields, K. Stoysich, R. Taylor, and A. L. Atkin, 2005. Upf1p, a highly conserved protein required for nonsense-mediated mRNA decay, interacts with the nuclear pore proteins Nup100p and Nup116p. Genes 345:199-212.
• Shields, C.M., R. Taylor, T. Nazarenus, J. Cheatle, A. Hou, A. Tapprich, A. Haifley, and A. L. Atkin, 2003. Saccharomyces cerevisiae Ats1p interacts with Nap1p, a cytoplasmic protein that controls bud morphogenesis. Current Genetics, 44:184-194.
• Kebaara, B., T. Nazarenus, R. Taylor, A. Forch, and A. L. Atkin, 2003. The Upf-dependent decay of wild-type PPR1 mRNA depends on its 5'-UTR and first 92 ORF nucleotides. Nucleic Acids Res. 31:3157-3165.
• Kebaara, B., T. Nazarenus, R. Taylor, and A. L. Atkin, 2003. Genetic background affects relative nonsense mRNA accumulation in wild-type and upf mutant yeast strains. Curr. Genet. 43:171-177
• Atkin, A. L., 1999. Preparation of yeast cells for confocal microscopy. Methods Mol. Biol. 122:131-139.
• J. N. Dahlseid, J. Puziss, R. L. Shirley, A. L. Atkin, P. Hieter, and M. R. Culbertson, 1998. Accumulation of mRNA Coding for yeast Ctf13 kinetocore subunit depends on the same factors that promote rapid decay of nonsense mRNAs. Genetics 150:1019-1035.
• Atkin, A. L., L. R. Schenkman, M. Eastham, J. D. Dahlseid, and M. R. Culbertson, 1997. Relationship between yeast polyribosomes and Upf proteins required for nonsense mRNA decay. J. Biol. Chem. 272:22163-22172.
• Atkin, A. L., N. Altamura, P. Leeds, and M. R. Culbertson, 1995. The majority of yeast UPF1 co-localizes with polyribosomes in the cytoplasm. Mol. Biol. Cell. 6:611-625.