HSF1 Modulation of Hsp70 mRNA Polyadenylation via Interaction with Symplekin

Hongyan Xing, Christopher N. Mayhew, Katherine E. Cullen, Ok Kyong Park-Sarge, Kevin D. Sarge

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Induction of heat shock protein (HSP) gene expression by stress is initiated by binding of HSF1 to HSP gene promoters to increase their transcription. The cytoprotective functions of these HSPs are essential for cell survival, and thus it is critical that inducible HSP gene expression be executed rapidly and efficiently. Here we report an interaction between heat shock factor 1 (HSF1) and symplekin, a protein known to form a complex with the polyadenylation factors CstF and CPSF. HSF1-symplekin complexes are detected only after stress treatment, and these two proteins co-localize in punctate nuclear structures in stressed cells. HSF1 also complexes in a stress-induced manner with the 3′ processing factor CstF-64. Interfering with HSF1-symplekin interaction by overexpressing a non-DNA-binding mutant HSF1 protein significantly decreases Hsp70 mRNA polyadenylation in stressed cells, supporting the functional role for HSF1 in promoting 3′ processing of this transcript. Importantly, this was also found to result in a significant loss of Hsp70 protein induction and increased cell death in response to stress exposure. These results indicate that the HSF1-symplekin interaction functions as a mechanism for recruiting polyadenylation factors to HSP genes to enhance the efficiency/kinetics of production of mature Hsp mRNA transcripts to achieve the critical cellular need for rapid HSP expression after stress. Thus, HSF1 regulates HSP gene expression at not one but two different steps of the expression pathway, functioning both as a transcription factor and a polyadenylation stimulatory factor.

Original languageEnglish
Pages (from-to)10551-10555
Number of pages5
JournalJournal of Biological Chemistry
Volume279
Issue number11
DOIs
StatePublished - Mar 12 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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