Developmental regulation of an organelle tether coordinates mitochondrial remodeling in meiosis.

Cellular differentiation involves remodeling cellular architecture to transform one cell type to another. By investigating mitochondrial dynamics during meiotic differentiation in budding yeast, we sought to understand how organelle morphogenesis is developmentally controlled in a system where regulators of differentiation and organelle architecture are known, but the interface between them remains unexplored. We analyzed the regulation of mitochondrial detachment from the cell cortex, a known meiotic alteration to mitochondrial morphology. We found that mitochondrial detachment is enabled by the programmed destruction of the mitochondria-endoplasmic reticulum-cortex anchor (MECA), an organelle tether that bridges mitochondria and the plasma membrane. MECA regulation is governed by a meiotic transcription factor, Ndt80, which promotes the activation of a conserved kinase, Ime2. We further present evidence for Ime2-dependent phosphorylation and degradation of MECA in a temporally controlled manner. Our study defines a key mechanism that coordinates mitochondrial morphogenesis with the landmark events of meiosis and demonstrates that cells can developmentally regulate tethering to induce organelle remodeling

Lifting All Boats: Fostering a Community of Practice for Student Publishers

Undergraduate and graduate students are increasingly being encouraged to work with faculty and researchers to generate traditional scholarship, as well as other types of projects that feature original content. Through this process, students are more frequently taking on roles as researchers, authors, and publishers. Student scholarship and student-run publications are valuable to the scholarly record, representing the nascent activities of the next generation of scholars, but also serving as an academic playground for emergent forms of publishing and media. Furthermore, students who manage publications gain practical skills that transfer to a variety of careers in academia and private industry. However, student publications are often struggling and are occasionally invisible. They face many of the same sustainability problems affecting the broader publishing industry, as well as unique problems inherent in student publications. These groups frequently need and often seek a combination of professional mentorship and a forum for peer group interactions to advance their publishing goals. At Georgetown University, Ohio University, and the University of Maryland, university presses and libraries have each leveraged their expertise and resources to research the student publishing landscape and develop a low-risk program to build a community of practice for student publications

Understanding crossover control using A. thaliana and S. cerevisiae

During meiosis, homologous chromosomes pair, synapse, and recombine to facilitate accurate chromosome segregation in meiosis I. Meiotic recombination is facilitated by programmed double-strand breaks that can be repaired either as crossovers or non-crossovers. In most organisms, crossover distribution along chromosomes is non-random in that crossovers are more evenly spaced than null expectations. The inhibition of closely spaced events is known as interference. Despite the fact that interference was originally observed almost a century ago, fundamental questions regarding its underlying mechanisms still exist. I discuss key unanswered questions regarding interference as well as the most commonly referenced models that have been proposed to explain the interference mechanism. We have developed a visual assay (the FTL system) for the detection of crossovers, gene conversions and interference in A. thaliana. This assay involves monitoring the segregation of fluorescent proteins in the pollen grains of qrt1 mutants. qrt1 mutants exhibit pollen tetrads i.e. the fusion of the four meiotic products, which allows for advanced statistical analyses previously only available in yeasts. The development and applications of this system are discussed. Humans, S. cerevisiae and A. thaliana have at least two pathways for producing crossovers, which include a primary pathway that is subject to interference and a secondary pathway that is interference-insensitive. Using the FTL system, we demonstrate that AtMUS81 is a mediator of the interference-insensitive pathway in A. thaliana. Atmus81 mutants are sensitive to a wide range of DNA damaging agents and exhibit decreased pollen viability and crossover frequency. The remaining crossovers in the Atmus81 mutant are subject to interference. Meiotic recombination occurs in the context of chromatin and chromatin context is often invoked to explain why recombination occurs preferentially in some genomic regions. Using a technique called FAIRE, we demonstrate that double-strand break hotspots and regions of open chromatin have a positive but complex association in S. cerevisiae. We also show that subtelomeric border regions and regions surrounding tRNA genes are enriched for meiosis-specific open chromatin. Centromeres exhibit constitutive enrichment of open chromatin

Genetic Interference: Dont Stand So Close to Me

Meiosis is a dynamic process during which chromosomes undergo condensation, pairing, crossing-over and disjunction. Stringent regulation of the distribution and quantity of meiotic crossovers is critical for proper chromosome segregation in many organisms. In humans, aberrant crossover placement and the failure to faithfully segregate meiotic chromosomes often results in severe genetic disorders such as Down syndrome and Edwards syndrome. In most sexually reproducing organisms, crossovers are more evenly spaced than would be expected from a random distribution. This phenomenon, termed interference, was first reported in the early 20th century by Drosophila geneticists and has been subsequently observed in a vast range of organisms from yeasts to humans. Yet, many questions regarding the behavior and mechanism of interference remain poorly understood. In this review, we examine results new and old, from a wide range of organisms, to begin to understand the progress and remaining challenges to understanding the fundamental unanswered questions regarding genetic interference

The Role of AtMUS81 in Interference-Insensitive Crossovers in A. thaliana

MUS81 is conserved among plants, animals, and fungi and is known to be involved in mitotic DNA damage repair and meiotic recombination. Here we present a functional characterization of the Arabidopsis thaliana homolog AtMUS81, which has a role in both mitotic and meiotic cells. The AtMUS81 transcript is produced in all tissues, but is elevated greater than 9-fold in the anthers and its levels are increased in response to gamma radiation and methyl methanesulfonate treatment. An Atmus81 transfer-DNA insertion mutant shows increased sensitivity to a wide range of DNA-damaging agents, confirming its role in mitotically proliferating cells. To examine its role in meiosis, we employed a pollen tetrad–based visual assay. Data from genetic intervals on Chromosomes 1 and 3 show that Atmus81 mutants have a moderate decrease in meiotic recombination. Importantly, measurements of recombination in a pair of adjacent intervals on Chromosome 5 demonstrate that the remaining crossovers in Atmus81 are interference sensitive, and that interference levels in the Atmus81 mutant are significantly greater than those in wild type. These data are consistent with the hypothesis that AtMUS81 is involved in a secondary subset of meiotic crossovers that are interference insensitive

Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis

Message-specific translational control is required for gametogenesis. In yeast, the RNA-binding protein Rim4 mediates translational repression of numerous mRNAs, including the B-type cyclin CLB3, which is essential for establishing the meiotic chromosome segregation pattern. Here, we show that Rim4 forms amyloid-like aggregates and that it is the amyloid-like form of Rim4 that is the active, translationally repressive form of the protein. Our data further show that Rim4 aggregation is a developmentally regulated process. Starvation induces the conversion of monomeric Rim4 into amyloid-like aggregates, thereby activating the protein to bring about repression of translation. At the onset of meiosis II, Rim4 aggregates are abruptly degraded allowing translation to commence. Although amyloids are best known for their role in the etiology of diseases such as Alzheimer’s, Parkinson’s, and diabetes by forming toxic protein aggregates, our findings show that cells can utilize amyloid-like protein aggregates to function as central regulators of gametogenesis.Charles A. King Trust (Postdoctoral Fellowship)American Cancer Society (Fellowship)National Institutes of Health (U.S.) (Grants GM62207, GM77537, and GM094303

Meiotic Cells Counteract Programmed Retrotransposon Activation via RNA-Binding Translational Repressor Assemblies

International audienceRetrotransposon proliferation poses a threat to germline integrity. While retrotransposons must be activated in developing germ cells in order to survive and propagate, how they are selectively activated in the context of meiosis is unclear. We demonstrate that the transcriptional activation of Ty3/Gypsy retrotransposons and host defense are controlled by master meiotic regulators. We show that budding yeast Ty3/Gypsy co-opts binding sites of the essential meiotic transcription factor Ndt80 upstream of the integration site, thereby tightly linking its transcriptional activation to meiotic progression. We also elucidate how yeast cells thwart Ty3/Gypsy proliferation by blocking translation of the retrotransposon mRNA using amyloid-like assemblies of the RNA-binding protein Rim4. In mammals, several inactive Ty3/Gypsy elements are undergoing domestication. We show that mammals utilize equivalent master meiotic regulators (Stra8, Mybl1, Dazl) to regulate Ty3/Gypsy-derived genes in developing gametes. Our findings inform how genes that are evolving from retrotransposons can build upon existing regulatory networks during domestication

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

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

News from Arabidopsis on the Meiotic Roles of Blap75/Rmi1 and Top3α

International audienc