title: 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.
authors.affiliation: Cancer Research UK Cell Cycle Genetics Group, University of Cambridge, Department of Genetics, Cambridge CB2 3EH, UK.
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Blagden
authors.forename: Melanie K
authors.initials: MK
authors.lastname: Gatt
authors.forename: Vincent
authors.initials: V
authors.lastname: Archambault
authors.forename: Karolina
authors.initials: K
authors.lastname: Lada
authors.forename: Keiko
authors.initials: K
authors.lastname: Ichihara
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Lilley
authors.forename: Yoshihiro H
authors.initials: YH
authors.lastname: Inoue
authors.forename: David M
authors.initials: DM
authors.lastname: Glover
mesh_terms: D000483:Alleles; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D047108:Embryonic Development / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000378:metabolism; D008297:Male; D008540:Meiosis; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C485865:Larp protein, Drosophila; C526781:Pabp protein, Drosophila; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins