An Important Role for RPRD1B in the Heat Shock Response

ABSTRACT

During the heat shock response (HSR), heat shock factor (HSF1 in mammals) binds to target gene promoters, resulting in increased expression of heat shock proteins that help maintain protein homeostasis and ensure cell survival. Besides HSF1, only a relatively few transcription factors with a specific role in ensuring correctly regulated gene expression during the HSR have been described. Here, we use proteomic and genomic (CRISPR) screening to identify a role for RPRD1B in the response to heat shock. Indeed, cells depleted for RPRD1B are heat shock sensitive and show decreased expression of key heat shock proteins (HSPs). These results add to our understanding of the connection between basic gene expression mechanisms and the HSR.

KEYWORDS:

• HSF
• HSF1
• RNA polymerase II
• RPRD1B
• heat shock
• transcription

Declaration of Interests

The authors declare no conflict of interest.

SUPPLEMENTAL MATERIAL

Supplemental material is available online only.

ACKNOWLEDGMENTS

This work was supported by the Francis Crick Institute (FCI receives funding from Cancer Research UK [FC001166], the UK Medical Research Council [FC001166], and the Welcome Trust [FC001166]), and by grants to J.Q.S. from the European Research Council (Agreement 693327), a Laureate grant from the Novo Nordisk Foundation (NNF19OC0055875), and a chair grant from the Danish National Research Foundation (DNRF153). We thank FCI’s Proteomics Facility, Advanced Sequencing Facility, and Cell Services for expert technical assistance; Paola Scaffidi for pLX-sg-nontargeting-A bunch plasmids; Dirk Eick for phospho RNAPII antibodies; Rocco D’Antuono from the Crick Advanced Microscopy Facility (CALM) for assistance with microscopy image acquisition; Barbara Dirac-Svejstrup for comments on the manuscript; and Svejstrup lab members for discussions.