Analyses of translation factors Dbp1 and Ded1 reveal the cellular response to heat stress to be separable from stress granule formation

Naohiro Kuwayama; Emily Nicole Powers; Matej Siketanc; Camila Ines Sousa; Kendra Reynaud; Marko Jovanovic; Maria Hondele; Nicholas Thomas Ingolia; Gloria Ann Brar

Cell Reports (Dec 2024)

Analyses of translation factors Dbp1 and Ded1 reveal the cellular response to heat stress to be separable from stress granule formation

Naohiro Kuwayama,
Emily Nicole Powers,
Matej Siketanc,
Camila Ines Sousa,
Kendra Reynaud,
Marko Jovanovic,
Maria Hondele,
Nicholas Thomas Ingolia,
Gloria Ann Brar

Affiliations

Naohiro Kuwayama: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Emily Nicole Powers: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Matej Siketanc: Biozentrum, Center for Molecular Life Sciences, University of Basel, 4056 Basel, Switzerland
Camila Ines Sousa: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Kendra Reynaud: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Marko Jovanovic: Department of Biological Sciences, Columbia University, New York, NY 10027, USA
Maria Hondele: Biozentrum, Center for Molecular Life Sciences, University of Basel, 4056 Basel, Switzerland
Nicholas Thomas Ingolia: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Gloria Ann Brar: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 12
p. 115059

Abstract

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Summary: Ded1 and Dbp1 are paralogous conserved DEAD-box ATPases involved in translation initiation in yeast. In long-term starvation states, Dbp1 expression increases and Ded1 decreases, whereas in cycling mitotic cells, Dbp1 is absent. Inserting DBP1 in place of DED1 cannot replace Ded1 function in supporting mitotic translation, partly due to inefficient translation of the DBP1 coding region. Global translation measurements, activity of mRNA-tethered proteins, and growth assays show that—even at matched protein levels—Ded1 is better than Dbp1 at activating translation, especially for mRNAs with structured 5′ leaders. Heat-stressed cells normally downregulate translation of structured housekeeping transcripts and halt growth, but neither occurs in Dbp1-expressing cells. This failure to halt growth in response to heat is not based on deficient stress granule formation or failure to reduce bulk translation. Rather, it depends on heat-triggered loss of Ded1 function mediated by an 11-amino-acid interval within its intrinsically disordered C terminus.

CP: Molecular biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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