title: Association of maternal mRNA and phosphorylated EIF4EBP1 variants with the spindle in mouse oocytes: localized translational control supporting female meiosis in mammals.
abstract: In contrast to other species, localized maternal mRNAs are not believed to be prominent features of mammalian oocytes. We find by cDNA microarray analysis enrichment for maternal mRNAs encoding spindle and other proteins on the mouse oocyte metaphase II (MII) spindle. We also find that the key translational regulator, EIF4EBP1, undergoes a dynamic and complex spatially regulated pattern of phosphorylation at sites that regulate its association with EIF4E and its ability to repress translation. These phosphorylation variants appear at different positions along the spindle at different stages of meiosis. These results indicate that dynamic spatially restricted patterns of EIF4EBP1 phosphorylation may promote localized mRNA translation to support spindle formation, maintenance, function, and other nearby processes. Regulated EIF4EBP1 phosphorylation at the spindle may help coordinate spindle formation with progression through the cell cycle. The discovery that EIF4EBP1 may be part of an overall mechanism that integrates and couples cell cycle progression to mRNA translation and subsequent spindle formation and function may be relevant to understanding mechanisms leading to diminished oocyte quality, and potential means of avoiding such defects. The localization of maternal mRNAs at the spindle is evolutionarily conserved between mammals and other vertebrates and is also seen in mitotic cells, indicating that EIF4EBP1 control of localized mRNA translation is likely key to correct segregation of genetic material across cell types.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Romasko
authors.forename: Dasari
authors.initials: D
authors.lastname: Amarnath
authors.forename: Uros
authors.initials: U
authors.lastname: Midic
authors.forename: Keith E
authors.initials: KE
authors.lastname: Latham
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics; D039642:Eukaryotic Initiation Factors; D005260:Female; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009865:Oocytes / Q000254:growth & development / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics*; D008941:Spindle Apparatus / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D010750:Phosphoproteins; D012333:RNA, Messenger
keywords: Microarray; cell cycle; localized maternal mRNA; meiosis, spindle; protein phosphorylation; translational control