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Michael Slevin


mslevin@email.unc.edu
Mentor: Rebecca Hartley, Ph.D.
Role of the 3’UTR and RNA binding proteins in the translational regulation of cyclin E during embryogenesis.

Currently I am employing a Xenopus laevis model system to investigate how alterations in cyclin E mRNA stability and translation affect the cell cycle. Prior investigation has shown that overexpression of cyclin E is correlated with the development of cancer in certain human tissues. One model that accounts for these observations is that an increase in cyclin E mRNA stability leads to overexpression of the protein, fostering dysregulation of the cell cycle. I have hypothesized that the 3’ untranslated region (3’ UTR) of cyclin E mRNAs contain cis-acting elements that are targets for RNA binding proteins, whose function is the regulation of cyclin E mRNA stability and translation. We have determined that HuR binds to the 3’UTR of cyclin E mRNA. HuR was first characterized as a tumor antigen and is an RNA binding protein that targets adenine and uridine rich sequences and functions to increase the stability of mRNA transcripts. I am currently testing whether an alteration of the 3’UTR of cyclin E will alter the ability of HuR to bind the transcript and if such an alteration decreases the adenylation state of the mRNA. I will also determine if such a change in adenylation/HuR binding affects the rate of cyclin E translation. Once I have determined the role of HuR in regulating cyclin E mRNA stability and translation I will test these findings in a human cancer model.

Abstracts:

Hughes, S.M., Brooks, A.I., Yang, G.S., Slevin, M., Haskell, R.E., Staber, P.D., and Davidson, B.L. FIV-Mediated Delivery of Differentiation Factors to Mouse Neural Progenitor Cells. 4th Annual Meeting of the American Society of Gene Therapy, 2001.

Boyle, B., Slevin, M., Audic, Y., and Hartley, R.S. Regulation and degradation of cyclin E in the early embryonic cell cycle. Society for Developmental Biology 60th Annual Meeting, 344. 2001.

Gourronc, F., Slevin, M., Garbrecht, M., and Hartley, R. Cyclin E translational control in the mechanism and regulation of the cell cycle in Xenopus embryo. Experimental Biology Meeting, 434.18. 2002.

Garbrecht, M., Gourronc, F., Slevin, M., Fritz, B., Sheets, M.D. and Hartley, R. Developmental Regulation of Cyclin mRNA Translation and Stability. Cold Spring Harbor Laboratory Symposium: Translational Control. 97. 2002.

Slevin, M., Gourronc, F., Garbrecht, M., and Hartley, R. Role of the 3’UTR in the translational regulation of cyclin E. 7th Annual Meeting of the RNA Society, 402. 2002.

Slevin, M., Lyons-Levy, G., Guo, X., and Hartley, R.S. Regulation of cyclin mRNAs during the embryonic to adult cell cycle transition. Experimental Biology Meeting: Translating the Genome. 849.2. 2003.

Lyons-Levy, G., Slevin, M., and Hartley, R.S. Translational silencing of cyclins following the midblastula transition. Keystone Symposia: Cell cycle and development. 55.220. 2004.

Slevin, M., Guo, X., Lyons-Levy, G., and Hartley, R.S. Cyclin mRNAs translation and stability ARE differentially regulated in the embryonic cell cycle. FASEB Summer Research Conferences: (Post-Transcriptional Control of Gene Expression: Mechanisms of mRNA Decay). 113. 2004

Publications:

Audic, Y., Boyle, B., Slevin, M., and Hartley, R.S. Cyclin E morpholino delays embryogenesis in Xenopus. Genesis 30:107-9, 2001.

Slevin, M.K., Lyons-Levy, G., Weeks, D.L., and Hartley, R.S. Antisense Knockdown of Cyclin E does not affect the Midblastula Transition in Xenopus laevis Embryos. Cell Cycle. Oct 18;4(10) 1396-1402, 2005.

Slevin, M.K., Gourronc, F., Hartley, R.S. ElrA binding to the 3'UTR of cyclin E1 mRNA requires polyadenylation elements. Nucleic Acids Res. 35(7):2167-76, 2007.



Honors and Awards

  • Presentations: Slevin, M, G Lyons-Levy, X Guo, RS Hartley, 2003. Regulation of cyclin mRNAs during