THE GAZETTE

What Is Frameshiftng And Antizyme?

The background of mRNA recoding has been studied in both prokaryotic and eukaryotic systems. A minority of mRNAs are able to undergo a process of temporary recoding, also called programmed alternate decoding. Recoding can occur by altering (1) the codon meaning (UAG to CAG, Stop to Gln); (2) the co-linearity (Bypassing); or (3) the reading frame (Frameshifting). The prokaryotic protein, Release factor 2 (rf2), is an example of recoding. The translation may either terminate at the stop codon or undergo a +1 frameshift to produce rf2.

Antizyme is another example of frame-shifting. The expression of antizyme requires programmed ribosomal frameshifting which is stimulated by polyamines. In the first step of polyamine biosynthesis, ornithine decarboxylase (ODC) catalyzes the conversion of ornithine to putrescine. The final polyamine products induce frame-shifting of antizyme which in turn targets ODC for degradation. Thus, the cell is able to regulate the amount of ODC through this autoregulatory mechanism. The importance of studying the polyamine pathway is that polyamines are essential for cell growth and are found in almost all eukaryotic cells. Cells and tissues that are undergoing rapid growth, e.g. cancer cells, usually have higher cellular polyamine concentration. Understanding the polyamine pathway and finding ways to manipulate cellular polyamine contents may be an essential step in controlling cellular growth.

The story of antizyme in D. melanogaster was a tangent of Ivaylo's research. He was searching the computer for homologous sequences to the highly conserved area that surrounded the site of antizyme frame-shifting. The Drosophila gene named gutfeeling which is responsible for muscle differentiation and the peripheral nerve system was identified as a possible homolog to antizyme. However, previous reports and a published paper seemed to oppose the possibility of gutfeeling as a potential antizyme. After Ivaylo performed several experiments showing obvious discrepancies with the published paper, it was concluded that the paper's Northern blot was mislabeled and the published sequence was missing a 66 nucleotide. ,P> Ivaylo's initial observation and continued follow-up is an excellent example of how a true "gutfeeling" changed science.

If you are interested in frameshifting and antizyme, you might want to check one of the papers from Ivaylo's lab: Matsufuji, S., Matsufuji, T., Miyazaki, Y., Murakami, Y., Atkins, J.F., Gesteland, R.F., and Hayashi, S. (1995). "Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme." Cell 80:51-60.

The slides showed a campus very similar to the University of Arizona. Both have the well-groomed, modern look of a west coast university with a view of the mountains. It, too, is surrounded by outdoor adventure -- hiking, camping, skiing. The Molecular Biology and Biochemistry graduate programs are combined. The departments support over 100 labs some of which have been recognized for their outstanding work in knock-out mice and human genetics. If you are interested in the University of Utah or have any questions, please contact Ivaylo at: ivaylo.ivanov@ m.cc.utah.edu.

After the lecture, Feliza Sibayan from Dr. Dieckmann's lab, Clare Ellsworth and Cherry Scriben from Dr. Pepperberg's lab in Ecology & Evolutionary Biology and I (Jessica Yingling) escorted Ivaylo to Sinbad's for some Mediterranean cuisine. We got the skinny on graduate school, discussed our graduation options and professional goals, and sampled a delicious mixture of foods suitable for both herbivores and carnivores.

Jessica Yingling, UBRPer in Dr. Gerner's Lab in Radiation Oncology

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