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

Berchowitz, Luke E.; Gajadhar, Aaron S.; Werven, Folkert J. van; Rosa, Alexandra A. De; Samoylova, Mariya L.; Brar, Gloria A.; Xu, Yaohui; Xiao, Che; Futcher, Bruce; Weissman, Jonathan S.; White, Forest M.; Amon, Angelika

doi:10.1101/gad.224253.113

Cited by 95 publications

(209 citation statements)

References 43 publications

(74 reference statements)

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“…Indeed, other Smk1/CDK parallels exist, including the activation of Smk1 by a CAK and the tight coupling of Ssp2 to specific stages of the cell cycle (in this case, exit from MII). In this regard, it is interesting that expression of the Clb3 cyclin and Ssp2 is controlled by the same transcription factor (Ndt80) and that the Rim4 translational repressor holds both CLB3 and SSP2 mRNAs inactive until translational derepression is triggered by Ime2 (35,36). In addition, similar to that of cyclin-CDKs, maximal phosphorylation of substrates by Ssp2/Smk1 requires residues (Ϫ4Y for Smk1) in addition to the minimal S/T-P site.…”

Section: Discussionmentioning

confidence: 99%

Ssp2 Binding Activates the Smk1 Mitogen-Activated Protein Kinase

Tio

Omerza

Phillips

et al. 2017

Molecular and Cellular Biology

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Smk1 is a meiosis-specific mitogen-activated protein kinase (MAPK) in Saccharomyces cerevisiae that couples spore morphogenesis to the completion of chromosome segregation. Similar to other MAPKs, Smk1 is controlled by phosphorylation of a threonine (T) and a tyrosine (Y) in its activation loop. However, it is not activated by a dual-specificity MAPK kinase. Instead, T207 in Smk1's activation loop is phosphorylated by the cyclin-dependent kinase (CDK)-activating kinase (Cak1), and Y209 is autophosphorylated in an intramolecular reaction that requires the meiosis-specific protein Ssp2. In this study, we show that Smk1 is catalytically inert unless it is bound by Ssp2. While Ssp2 binding activates Smk1 by a mechanism that is independent of activation loop phosphorylation, binding also triggers autophosphorylation of Y209 in Smk1, which, along with Cak1-mediated phosphorylation of T207, further activates the kinase. Autophosphorylation of Smk1 on Y209 also appears to modify the specificity of the MAPK by suppressing Y kinase and enhancing S/T kinase activity. We also found that the phosphoconsensus motif preference of Ssp2/Smk1 is more extensive than that of other characterized MAPKs. This study therefore defines a novel mechanism of MAPK activation requiring binding of an activator and also shows that MAPKs can be diversified to recognize unique phosphorylation motifs.

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Section: Discussionmentioning

confidence: 99%

Ssp2 Binding Activates the Smk1 Mitogen-Activated Protein Kinase

Tio

Omerza

Phillips

et al. 2017

Molecular and Cellular Biology

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“…The timing of Sps1 protein accumulation is governed by an Ime2/ Rim4-dependent translational repression and derepression that delays Sps1 production until after MII, despite SPS1 transcription occurring at MI with Ndt80-MSE induction (Berchowitz et al 2013). Whatever activates Sps1 may represent an additional signal monitoring the state of the cell, whose output is used to decide when cytokinesis occurs.…”

Section: Discussionmentioning

confidence: 99%

Timely Closure of the Prospore Membrane Requires SPS1 and SPO77 in Saccharomyces cerevisiae

et al. 2016

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During sporulation in Saccharomyces cerevisiae, a double lipid bilayer called the prospore membrane is formed de novo, growing around each meiotic nucleus and ultimately closing to create four new cells within the mother cell. Here we show that SPS1, which encodes a kinase belonging to the germinal center kinase III family, is involved in prospore membrane development and is required for prospore membrane closure. We find that SPS1 genetically interacts with SPO77 and see that loss of either gene disrupts prospore membrane closure in a similar fashion. Specifically, cells lacking SPS1 and SPO77 produce hyperelongated prospore membranes from which the leading edge protein complex is not removed from the prospore membrane in a timely fashion. The SPS1/ SPO77 pathway is required for the proper phosphorylation and stability of Ssp1, a member of the leading edge protein complex that is removed and degraded when the prospore membrane closes. Genetic dissection of prospore membrane closure finds SPS1 and SPO77 act in parallel to a previously described pathway of prospore membrane closure that involves AMA1, an activator of the meiotic anaphase promoting complex.KEYWORDS prospore membrane; meiotic exit; anaphase promoting complex; sporulation; cytokinesis; germinal center kinase B IOLOGICAL membranes provide a barrier for inhibiting the flow of materials between a cell and its surroundings and for compartmentalizing the contents of the various organelles within a cell. The size and shape of membranes are central to their functions. Membranes are essential for many fundamental cellular processes including ion balance, energy generation, and secretion. In cell division, membrane dynamics are particularly important, where they act to segregate the contents of the cellular progeny.The process of cell division differs among cells. Most commonly, animal cells divide through a mechanism requiring the assembly of an actin-based contractile ring at the division site (reviewed in Green et al. 2012). This actomyosin ring contracts and matures, ultimately leading to scission of the membrane necks mediated by the ESCRTIII (endosomal sorting complex required for transport III) complex. However, other variations of cytokinesis occur: cellularization during early Drosophila embryogenesis, which requires the growth of membranes around the nuclei before the contractile event (Lee and Harris 2014) and cell division in plants, which requires the secretion of vesicles to the division plane to form the phragmoplast, which will eventually separate the two daughter cells (reviewed in Jürgens 2005). Actin is not always involved in cytokinesis; although prokaryotic cells have actin-like filaments (reviewed in Carballido-López 2006), these filaments are not used for cytokinesis (Pollard and Wu 2010). Similarly, cytokinesis in Trypanosoma brucei (a bikont eukaryote) does not require actin but seems to utilize microtubules (Wheeler et al. 2013). In the budding yeast Saccharomyces cerevisiae, an actin-based contractile ring plays a role in ...

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“…This pathway involves the Ime2 kinase and the RNA binding protein Rim4 (16). Binding of Rim4 to the 5= untranslated region (UTR) of the CLB3 transcript represses CLB3 translation (15). Ime2 activity increases as cells progress through the meiotic divisions (13).…”

mentioning

confidence: 99%

“…A regulatory pathway has been defined that controls a set of transcripts, including CLB3 and SPO20, that are delayed in translation until the onset of meiosis II (15). This pathway involves the Ime2 kinase and the RNA binding protein Rim4 (16).…”

mentioning

confidence: 99%

“…However, after meiotic prophase, the fine control of the timing of gene expression appears to be performed predominantly at the level of translational regulation rather than transcription (12). To obtain the high degree of synchrony necessary to distinguish differences in timing of translation during the meiotic divisions, an inducible NDT80 system (NDT80-IN) was used for ribosome-profiling studies (13)(14)(15). NDT80-IN results from the combination of NDT80 fused to the GAL1 promoter and the presence of a GAL4-estradiol receptor gene (ER) fusion gene (13).…”

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confidence: 99%

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Sequestration of mRNAs Modulates the Timing of Translation during Meiosis in Budding Yeast

Jin

Zhang

et al. 2015

Molecular and Cellular Biology

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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...

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

Cited by 95 publications

References 43 publications

Ssp2 Binding Activates the Smk1 Mitogen-Activated Protein Kinase

Ssp2 Binding Activates the Smk1 Mitogen-Activated Protein Kinase

Timely Closure of the Prospore Membrane Requires SPS1 and SPO77 in Saccharomyces cerevisiae

Sequestration of mRNAs Modulates the Timing of Translation during Meiosis in Budding Yeast

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