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Published October 1, 2009 | Supplemental Material
Journal Article Open

Drosophila Larp associates with poly(A)-binding protein and is required for male fertility and syncytial embryo development

Abstract

As the influence of mRNA translation upon cell cycle regulation becomes clearer, we searched for genes that might specify such control in Drosophila. A maternal-effect lethal screen identified mutants in the Drosophila gene for Larp (La-related protein) which displayed maternal-effect lethality and male sterility. A role for La protein has already been implicated in mRNA translation whereas Larp has been proposed to regulate mRNA stability. Here we demonstrate that Larp exists in a physical complex with, and also interacts genetically with, the translation regulator poly(A)-binding protein (PABP). Most mutant alleles of pAbp are embryonic lethal. However hypomorphic pAbp alleles show similar meiotic defects to larp mutants. We find that larp mutant-derived syncytial embryos show a range of mitotic phenotypes, including failure of centrosomes to migrate around the nuclear envelope, detachment of centrosomes from spindle poles, the formation of multipolar spindle arrays and cytokinetic defects. We discuss why the syncytial mitotic cycles and male meiosis should have a particularly sensitive requirement for Larp proteins in regulating not only transcript stability but also potentially the translation of mRNAs.

Additional Information

© 2009 Elsevier Under an Elsevier user license. Received 2 February 2009, Revised 2 July 2009, Accepted 14 July 2009, Available online 22 July 2009. We thank Svenja Hester and Janusz Debski for technical work with the mass spectrometry and Renata Feret for invaluable assistance with 2D gels We thank Monica Bettencourt-Dias and Tetsuya Takeda for discussion and comments on the manuscript and the Bloomington and Szeged Stock Centres for fly stocks. Cancer Research UK provided support to SPB and DMG. DMG also received MRC Program Grant support for part of this work. KSL and DMG were supported by BBSRC Project Grants. VA was supported by long-term fellowships from the European Molecular Biology Organization and from the Human Frontier Science Program.

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