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

Autor: Naohiro Kuwayama, Emily Nicole Powers, Matej Siketanc, Camila Ines Sousa, Kendra Reynaud, Marko Jovanovic, Maria Hondele, Nicholas Thomas Ingolia, Gloria Ann Brar
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cell Reports, Vol 43, Iss 12, Pp 115059- (2024)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2024.115059
Popis: 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.
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