A developmentally regulated translational control pathway establishes the meiotic chromosome segregation pattern

• Main Authors: Berchowitz, Luke Edwin (Contributor), Gajadhar, Aaron (Contributor), van Werven, Folkert J. (Contributor), De Rosa, Alexandra A. (Contributor), Samoylova, Mariya L. (Contributor), Brar, Gloria A. (Author), Xu, Yifeng (Author), Xiao, Che (Author), Futcher, Bruce (Author), Weissman, Jonathan S. (Author), White, Forest M. (Contributor), Amon, Angelika B (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor), Amon, Angelika B. (Contributor)
• Format: Article
• Language: English
• Published: Cold Spring Harbor Laboratory Press, 2014-08-26T12:24:48Z.
• Subjects: Article
• Online Access: Get fulltext

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.
American Cancer Society (Post-doctoral Fellowship)
Virginia and D.K. Ludwig Fund for Cancer Research (Post-doctoral Fellowship)
National Institutes of Health (U.S.) (Grant GM62207)