Dual roles for PARP1 during heat shock: transcriptional activator and posttranscriptional inhibitor of gene expression. Molecular cell

In this issue of Molecular Cell, Di Giammartino et al. (2012) identify a new function for PARP1 in the post-transcriptional regulation of mRNAs via ADP-ribosylation of poly(A) polymerase, a mRNA 3 ′ processing enzyme. Poly(ADP-ribose) polymerase 1 (PARP1, also known as ARTD1) is an abundant nuclear protein that covalently modifies target proteins with poly(ADP-ribose) (PAR) using NAD+ as a substrate. It is a multifunctional enzyme and has many DNA-related nuclear functions including DNA damage repair and transcriptional regulation under normal and stressed conditions (reviewed in Kraus, 2008; Luo and Kraus, 2012). During heat shock a small number of genes, referred to as stress-responsive genes, are upregulated, although overall gene expression is downregulated. PARP1 plays a critical role in this upregulation by mediating the transcriptional activation of Hsp70 genes (Tulin and Spradling, 2003). This occurs at Hsp70 loci where PARP1 becomes activated during heat shock and modifies itself and histones, resulting in PARP1 release from chromatin and the loss of nucleosomes within Hsp70 coding regions (Ouararhni et al., 2006; Petesch and Lis, 2008, 2012). In this issue, D