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Angus M. MacNicol, Ph.D.
Angus M. MacNicol, Ph.D. Title
Associate Professor

PhD
University of London

Research Interests
Regulated mRNA translation is emerging as a key mechanism to control cell cycle progression during development and in the adult organism. Recent evidence has underscored the importance of regulatory elements in the 3’ untranslated region (3’ UTR) in mediating mRNA translational control in a variety of species and cellular processes including synaptic plasticity, neural stem cell self renewal and control of vertebrate oocyte maturation. Aberrant mRNA translational regulation may contribute to birth defects, infertility, tumor stem cell proliferation and cognitive dysfunction. The goal of the research in my lab is to understand the role of regulated mRNA translation in the control of cell cycle progression in both physiological and pathological contexts. We utilize oocytes of the frog Xenopus, as well as mammalian neural progenitor/stem cells and tumor cell lines to understand the role of regulated mRNA translation in cell cycle progression and stem cell self renewal. Developmentally, oocytes can be considered the “mother of all stem cells” and are predicted to share common properties of cell cycle regulation with adult stem cells. Indeed, we have recently discovered that the neural stem cell self renewal factor Musashi also regulates cell cycle progression during Xenopus oocyte maturation. While Musashi has been shown to be a sequence-specific RNA binding protein, the mechanism by which Musashi exerts mRNA translational control and the specific target mRNAs involved in cell cycle regulation and differentiation remain to be elucidated. Musashi is up-regulated in a variety of brain, breast and intestinal tumors and for certain tumors the malignancy of the tumor has been correlated with the levels of Musashi expression. We hypothesize that in cancer stem cells, or proliferating progenitor populations in tumors, elevated Musashi expression drives a self renewal program that facilitates tumor progression and maintenance. We believe a detailed understanding of the role, regulation and mRNA targets of Musashi under physiological conditions will present novel targets for therapeutic intervention in the treatment of human cancers.

Email: Angus@uams.edu

Address: Dept. of Neurobiology and Developmental Sciences,
and the Winthrop P. Rockefeller Cancer Institute,
University of Arkansas for Medical Sciences,
4301 W. Markham St. Slot 814,
Little Rock, AR 72205

Phone: 501-686-8164

Fax: 501-686-6517


Selected Publications
Charlesworth, A., Ridge, J.A., King, L.A., MacNicol, M.C., and MacNicol, A.M. 2002. A novel regulatory element determines the timing of Mos mRNA translation during Xenopus oocyte maturation. EMBO J. 21:2798-2806.

Charlesworth, A., Cox, L.L., and MacNicol, A.M. 2004. Cytoplasmic polyadenylation element (CPE)- and CPE-binding protein (CPEB)-independent mechanisms regulate early class maternal mRNA translational activation in Xenopus oocytes. J Biol Chem. 279:17650-17659.

Charlesworth, A., Wilczynska, A., Thampi, P., Cox, L.L., and MacNicol, A.M. 2006. Musashi regulates the temporal order of mRNA translation during Xenopus oocyte maturation. EMBO J. 25:2792-2801.

Prasad, C.K., Mahadevan, M., MacNicol, M.C. and MacNicol, A.M. 2008. Mos 3’ UTR regulatory differences underlie species-specific temporal patterns of Mos mRNA cytoplasmic polyadenylation and translational recruitment during oocyte maturation. Molecular Reproduction and Development 75:1258-68

Wang, Y., Charlesworth, A., Byrd, S.M., Gregerson, R., MacNicol, M.C. and MacNicol, A.M. 2008. A novel 3’ UTR translational control sequence regulates Xenopus Wee1 mRNA translation. Dev. Biol. 317: 454–466.

MacNicol, A.M., Wilczynska, A. and MacNicol, M.C. 2008. Function and regulation of the mammalian Musashi mRNA translational regulator. Biochemical Society Transactions 36:528-530.

Link to Dr. MacNicol's PubMed publications


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