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Paul M Macdonald
How mRNAs become localized within cells, and how their translation is regulated-
Research Summary:
A key challenge in biology is understanding how proteins are directed to the subcellular domains in which they function. We use Drosophila to address this question, focusing on factors localized to restricted regions of the oocyte, where they initiate events that specify the spatial organization of the embryo. The large size of the oocyte, together with the wealth of powerful genetic approaches using Drosophila, offers many advantages for mechanistic studies.
Our work has provided basic insights into the roles of mRNA localization and translational regulation in controlling subcellular protein localization. Current projects address the mechanisms of translational repression and activation, and how translational activation is coordinated with mRNA localization to achieve highly restricted protein distributions.
In addition, we are studying a remarkable phenomenon we recently discovered: some translational control elements can act in trans, with the regulatory elements within one mRNA affecting the expression of other mRNAs. We hypothesize that regulation in trans is made possible by assembly of mRNAs into particles, in which close proximity allows communication between mRNAs.
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Publications:
Macdonald, P.M., Kanke, M., and Kenny, A. (2016) Community effects in regulation of translation. eLife, in press.
Kim, G., Pai, C.-I., Sato, K., Person, M., Nakamura, A. and Macdonald, P.M. (2015) Region-specific activation of oskar mRNA translation by inhibition of Bruno-mediated repression. PLoS Genetics, doi 10.1371/journal.pgen.1004992.
Kanke, M., Jambor, H., Reich, J., Marches, B., Gstir, R., Ryu, Y.H., Ephrussi, A., and Macdonald, P.M. (2015) oskar RNA plays multiple non-protein coding roles to support oogenesis and maintain integrity of the germline/soma distinction. RNA 21, 1096-1109.
Kanke, M. and Macdonald, P.M. (2015) Translational activation of oskar mRNA: reevaluation of the role and importance of a 5' regulatory element. PLoS One 10, e01258.
Jones, J. and Macdonald, P.M. (2015) Neurl4 contributes to germ cell formation and integrity in Drosophila. Biology Open 4, 937-946.
Ryu, Y.H. and Macdonald, P.M. (2015) RNA Sequences Required for the Noncoding Function of oskar RNA also Mediate Regulation of Oskar Protein Expression by Bicoid Stability Factor. Developmental Biology 407, 211-223.
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