Autophagy of an Amyloid-like Translational Repressor Regulates Meiotic Exit
We explored the potential for autophagy to regulate budding yeast meiosis. Following pre-meiotic DNA replication, we blocked autophagy by chemical inhibition of Atg1 kinase or engineered degradation of Atg14 and observed homologous chromosome segregation followed by sister chromatid separation; cell...
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Published in | Developmental cell Vol. 52; no. 2; pp. 141 - 151.e5 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
27.01.2020
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Subjects | |
Online Access | Get full text |
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Summary: | We explored the potential for autophagy to regulate budding yeast meiosis. Following pre-meiotic DNA replication, we blocked autophagy by chemical inhibition of Atg1 kinase or engineered degradation of Atg14 and observed homologous chromosome segregation followed by sister chromatid separation; cells then underwent additional rounds of spindle formation and disassembly without DNA re-replication, leading to aberrant chromosome segregation. Analysis of cell-cycle regulators revealed that autophagy inhibition prevents meiosis II-specific expression of Clb3 and leads to the aberrant persistence of Clb1 and Cdc5, two substrates of a meiotic ubiquitin ligase activated by Ama1. Lastly, we found that during meiosis II, autophagy degrades Rim4, an amyloid-like translational repressor whose timed clearance regulates protein production from its mRNA targets, which include CLB3 and AMA1. Strikingly, engineered Clb3 or Ama1 production restored meiotic termination in the absence of autophagy. Thus, autophagy destroys a master regulator of meiotic gene expression to enable irreversible meiotic exit.
•Autophagy is required for meiotic exit•Autophagy prevents additional rounds of chromosome segregation after meiosis II•Autophagy degrades the amyloid-like translational repressor Rim4 in meiosis II•Inhibition of autophagy leads to aberrant persistence of meiotic regulators
Wang et al. report that autophagy promotes meiotic termination by degrading Rim4, an amyloid-like translational repressor whose timed clearance in meiosis II regulates protein production from its mRNA targets. In the absence of autophagy, cells fail to exit meiosis and undergo additional rounds of chromosome segregation after meiosis II. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author Contributions: SL, FW, and VD designed the experiments, analyzed the data, wrote the paper, and directed the project. SL, FW, RZ, WF, DT, OB, JL constructed yeast strains and performed the experiments. |
ISSN: | 1534-5807 1878-1551 |
DOI: | 10.1016/j.devcel.2019.12.017 |