Blagden Sarah P, Gatt Melanie K, Archambault Vincent, Lada Karolina, Ichihara Keiko, Lilley Kathryn S, Inoue Yoshihiro H, Glover David M
Cancer Research UK Cell Cycle Genetics Group, University of Cambridge, Department of Genetics, Cambridge CB2 3EH, UK.
Dev Biol. 2009 Oct 1;334(1):186-97. doi: 10.1016/j.ydbio.2009.07.016. Epub 2009 Jul 22.
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.
随着信使核糖核酸（mRNA）翻译对细胞周期调控的影响日益清晰，我们在果蝇中寻找可能参与此类调控的基因。一项母性效应致死筛选鉴定出果蝇Larp（La相关蛋白）基因的突变体，这些突变体表现出母性效应致死和雄性不育。La蛋白的作用已与mRNA翻译相关，而Larp则被认为可调节mRNA稳定性。在此我们证明，Larp与翻译调节因子聚腺苷酸结合蛋白（PABP）存在物理复合物，并在遗传上相互作用。大多数pAbp突变等位基因是胚胎致死的。然而，亚效pAbp等位基因表现出与larp突变体相似的减数分裂缺陷。我们发现，源自larp突变体的合胞体胚胎表现出一系列有丝分裂表型，包括中心体无法围绕核膜迁移、中心体从纺锤体极脱离、多极纺锤体阵列的形成以及胞质分裂缺陷。我们讨论了为什么合胞体有丝分裂周期和雄性减数分裂在调节转录本稳定性以及潜在的mRNA翻译方面对Larp蛋白有特别敏感的需求。
