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 59 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.

Highlights d Subcellular localization of conserved lncRNAs is different in hESCs and mESCs d Cytoplasmic hFAST but not nuclear mFast promotes WNT signaling in hESC pluripotency d PPIE regulates distinct FAST processing in hESCs and mESCs d RNA processing and localization contribute to lncRNA functional evolution

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bStarvation of diploid cells of the budding yeast Saccharomyces cerevisiae induces them to enter meiosis and differentiate into haploid spores. During meiosis, the precise timing of gene expression is controlled at the level of transcription, and also translation. If cells are returned to rich medium after they have committed to meiosis, the transcript levels of most meiotically upregulated genes decrease rapidly. However, for a subset of transcripts whose translation is delayed until the end of meiosis II, termed protected transcripts, the transcript levels remain stable even after nutrients are reintroduced. The Ime2-Rim4 regulatory circuit controls both the delayed translation and the stability of protected transcripts. These protected mRNAs localize in discrete foci, which are not seen for transcripts of genes with different translational timing and are regulated by Ime2. These results suggest that Ime2 and Rim4 broadly regulate translational delay but that additional factors, such as mRNA localization, modulate this delay to tune the timing of gene expression to developmental transitions during sporulation. Formation of haploid gametes from diploid cells through the specialized cell division of meiosis is central to the life cycle of sexually reproducing organisms. Gametogenesis involves exit from the mitotic cell cycle, progression through the meiotic divisions, and differentiation into specialized gametes that can later undergo fertilization to restore diploidy. In Saccharomyces cerevisiae gametogenesis, haploid genomes are packaged into gametes called spores, and the process is referred to as sporulation. Shared characteristics of sporulation and gametogenesis in metazoans include the dynamics of chromosome behavior in the meiotic prophase, postmeiotic hypercondensation of chromatin, and generation of specialized gametes (1-3).Sporulation is triggered by nitrogen starvation in the presence of a poor carbon source (1). These starvation signals lead to the transcription of IME1, which encodes a transcription factor that controls entry into meiosis (4). Ime1 induces expression of a set of genes that are required for premeiotic DNA synthesis, as well as the initial steps of meiosis, particularly those involved in recombination during the meiotic prophase (5, 6). A key target of Ime1 is the gene encoding the Ime2 protein kinase (4, 7). The combined action of Ime1 and Ime2 leads to the induction of a second transcription factor, encoded by NDT80 (8). Ndt80 upregulates its own expression, as well as that of ϳ300 additional genes termed the NDT80 regulon (8, 9). This regulon includes genes required for entry into the meiotic divisions, and thus, deletion of NDT80 results in the arrest of cells in the meiotic prophase (8, 10). NDT80 also governs the induction of genes whose products are required for late meiosis events, such as the packaging of daughter nuclei into spores, and postmeiotic events, such as spore wall development (9).After induction of the NDT80 regulon, there are two other temporally regulated sets...