Condensation of Ded1p Promotes a Translational Switch from Housekeeping to Stress Protein Production.

First Authors Christiane Iserman
Authors Christiane Iserman, Christine Desroches Altamirano, Ceciel Jegers, Ulrike Friedrich, Taraneh Zarin, Anatol Fritsch, Matthäus Mittasch, Antonio Domingues, Lena Hersemann, Marcus Jahnel, Doris Richter, Ulf-Peter Guenther, Matthias W. Hentze, Alan M Moses, Anthony Hyman, Günter Kramer, Moritz Kreysing, Titus Franzmann, Simon Alberti
Corresponding Authors Simon Alberti
Last Authors Simon Alberti
Journal Name Cell (Cell)
Volume 181
Issue 4
Page Range 818-831
Open Access true
Print Publication Date 2020-05-14
Online Publication Date
Abstract Cells sense elevated temperatures and mount an adaptive heat shock response that involves changes in gene expression, but the underlying mechanisms, particularly on the level of translation, remain unknown. Here we report that, in budding yeast, the essential translation initiation factor Ded1p undergoes heat-induced phase separation into gel-like condensates. Using ribosome profiling and an in vitro translation assay, we reveal that condensate formation inactivates Ded1p and represses translation of housekeeping mRNAs while promoting translation of stress mRNAs. Testing a variant of Ded1p with altered phase behavior as well as Ded1p homologs from diverse species, we demonstrate that Ded1p condensation is adaptive and fine-tuned to the maximum growth temperature of the respective organism. We conclude that Ded1p condensation is an integral part of an extended heat shock response that selectively represses translation of housekeeping mRNAs to promote survival under conditions of severe heat stress.
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Affiliated With Alberti, CSBD, Hyman, Kreysing, Postdocs, Predoc first author, Predoc first female, Scientific Computing Facility
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Acknowledged Services Technology Development Studio TDS, Protein Expression, Scientific Computing Facility, Light Microscopy Facility, FACS Facility
Publication Status Published
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DOI 10.1016/j.cell.2020.04.009
PubMed ID 32359423
WebOfScience Link WOS:000533623900009
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Created By thuem
Added Date 2020-05-05
Last Edited By herbst
Last Edited Date 2022-03-03 15:03:24.927
Library ID 7664
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