Dr Liz Poole

Senior Research Fellow
Poole
  • Biochemistry Department
  • School of Medical Sciences
  • University of Otago
  • P.O. Box 56
  • 710 Cumberland St
  • Dunedin 9054 , New Zealand
  • Tel.: +64 3 479-7841
  • FAX: +64 3 479-7866
  • e-mail:elizabeth.poole@otago.ac.nz
Recoding in mammalian Paternally Expressed Gene 10 (PEG10):

While investigating recoding in HIV, we found that an unusual human gene (PEG10) uses the same extremely rare ‘frameshift’ mechanism to make two proteins from one piece of its genetic information. Expression of the second PEG10 protein requires frameshifting and is precisely regulated. It may be synthesised only in placenta and surrounding tissues implying the second protein must have an important function in placental development. Significantly, PEG10 also functions as an oncogene for a variety of cancers and studies suggest that it might have a wider role in the regulation of cell proliferation and differentiation. We are investigating whether the frameshifted protein is important for these processes, how the gene is regulated, and in which tissues it is expressed.

Recoding in HIV:

Medical interventions against HIV use antiretroviral drugs that block viral replication at different sites of the HIV life-cycle. The drugs to date focus on the disruption of the viral reverse transcriptase and protease enzymes. New approaches to drug development are needed for several reasons; HIV has become a ‘chronic infection’ in Western countries although it still has lethal consequences in developing nations. Long-term therapy not only facilitates the development of drug resistance and viral persistence, but also produces unpleasant or serious side-affects.

Another vulnerable step in the lifecycle of HIV is a highly conserved but rare mechanism called frameshifting that ensures that the synthesis of its structural and enzymatic proteins are in the correct ratio essential for productive viral infection. In collaboration with Professor Warren Tate, we are investigating ways of disrupting this unique viral protein synthesis event by targeting a host function, the ribosome. An approach that targets the host may be more effective in delaying HIV resistance to potential drugs rather than targeting specific viral components.

Current Funding:

Marsden Fund of New Zealand
University of Otago Research Grant

Selected Publications:

Mathew, SF., Graves, R., Cardno, TS., McKinney, CZ., Poole, ES., Tate, WP. A highly conserved codon following the slippery sequence in the HIV-1 frameshift element modulates -1 frameshifting. (submitted)

Cardno, TS., Poole, ES., Mathew, SF., Graves, R., Tate, WP. A homogeneous cell-based bicistronic fluorescence assay for high-throughput identification of drugs that perturb viral gene recoding and read-through of nonsense stop codons. RNA 15:1614-1621 (2009)

Clark, M., Jänicke, M., Gottesburen, U., Kleffmann, T., Legge, M., Poole, E., Tate, W. Mammalian gene PEG10 expresses two reading frames by high efficiency –1 frameshifting in embryonic-associated tissues. Journal of Biological Chemistry 282:37359-37369 (2007)

Poole, E.S., Young, D.J., Askarian-Amiri, M.E., Debbie-Jane G. Scarlett, D-J.G., Tate, W.P. Accommodating the bacterial decoding release factor as an alien protein among the RNAs at the active site of the ribosome. Cell Research 17:591-607 (2007)

Cridge, A.G., Major, L.L., Mahagaonkar, A.A., Poole, E.S., Isaksson, L.A., Tate, W.P. Comparison of characteristics and function of translation termination signals between and within prokaryotic and eukaryotic organisms. Nucleic Acids Research 34:1959-1973 (2006)

Poole, E. S., Major, L. L., Cridge, A. G. and Tate, W. P. The mechanism of recoding in pro- and eukaryotes. In Protein Synthesis and Ribosome Structure: Translating the Genome K. Nierhaus, D. N. Wilson, Eds. Wiley-VCH, Weinheim, Germany (2004) pp397-428.

Tate, W. P. and Poole, E. S. The ribosome: lifting the veil from a fascinating organelle. BioEssays 26:582-588 (2004)

Poole, E. S., Askarian-Amiri, M. E., Major, L. L., McCaughan, K. K., Scarlett, D-J, G., Wilson, D. N. and Tate, W. P. Molecular mimicry in the decoding of translational stop signals. In Progress in Nucleic Acids Research and Molecular Biology 74:83-121 (2003)