title: A developmentally regulated translational control pathway establishes the meiotic chromosome segregation pattern.
abstract: Production of haploid gametes from diploid progenitor cells is mediated by a specialized cell division, meiosis, where two divisions, meiosis I and II, follow a single S phase. Errors in progression from meiosis I to meiosis II lead to aneuploid and polyploid gametes, but the regulatory mechanisms controlling this transition are poorly understood. Here, we demonstrate that the conserved kinase Ime2 regulates the timing and order of the meiotic divisions by controlling translation. Ime2 coordinates translational activation of a cluster of genes at the meiosis I-meiosis II transition, including the critical determinant of the meiotic chromosome segregation pattern CLB3. We further show that Ime2 mediates translational control through the meiosis-specific RNA-binding protein Rim4. Rim4 inhibits translation of CLB3 during meiosis I by interacting with the 5' untranslated region (UTR) of CLB3. At the onset of meiosis II, Ime2 kinase activity rises and triggers a decrease in Rim4 protein levels, thereby alleviating translational repression. Our results elucidate a novel developmentally regulated translational control pathway that establishes the meiotic chromosome segregation pattern.
authors.affiliation: Koch Institute for Integrative Cancer Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
authors.forename: Luke E
authors.initials: LE
authors.lastname: Berchowitz
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Gajadhar
authors.forename: Folkert J
authors.initials: FJ
authors.lastname: van Werven
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: De Rosa
authors.forename: Mariya L
authors.initials: ML
authors.lastname: Samoylova
authors.forename: Gloria A
authors.initials: GA
authors.lastname: Brar
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Xu
authors.forename: Che
authors.initials: C
authors.lastname: Xiao
authors.forename: Bruce
authors.initials: B
authors.lastname: Futcher
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Weissman
authors.forename: Forest M
authors.initials: FM
authors.lastname: White
authors.forename: Angelika
authors.initials: A
authors.lastname: Amon
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D047908:Intracellular Signaling Peptides and Proteins; D008540:Meiosis / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C064979:IME2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases
keywords: RNA-binding protein; cyclins; gametogenesis; kinase; meiosis; translational control; untranslated region