TheESS1Prolyl Isomerase and Its SuppressorBYE1Interact With RNA Pol II to Inhibit Transcription Elongation inSaccharomyces cerevisiae

Abstract

Transcription by RNA polymerase II (pol II) requires the ordered binding of distinct protein complexes to catalyze initiation, elongation, termination, and coupled mRNA processing events. One or more proteins from each complex are known to bind pol II via the carboxy-terminal domain (CTD) of the largest subunit, Rpb1. How binding is coordinated is not known, but it might involve conformational changes in the CTD induced by the Ess1 peptidyl-prolyl cis/trans isomerase. Here, we examined the role of ESS1 in transcription by studying one of its multicopy suppressors, BYE1. We found that Bye1 is a negative regulator of transcription elongation. This led to the finding that Ess1 also inhibits elongation; Ess1 opposes elongation factors Dst1 and Spt4/5, and overexpression of ESS1 makes cells more sensitive to the elongation inhibitor 6-AU. In reporter gene assays, ess1 mutations reduce the ability of elongation-arrest sites to stall polymerase. We also show that Ess1 acts positively in transcription termination, independent of its role in elongation. We propose that Ess1-induced conformational changes attenuate pol II elongation and help coordinate the ordered assembly of protein complexes on the CTD. In this way, Ess1 might regulate the transition between multiple steps of transcription.

PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC

“…Another SPOC domain protein, RBM15, regulates N 6 -methyladenosine (m6A) RNA modification, splicing, and mRNA export, and inhibits myeloid differentiation 76 – 79 . The yeast PHF3 homolog Bye1 negatively regulates early stages of transcription elongation 32 , 80 , while Arabidopsis SPOC proteins FPA and BORDER regulate 3′end pausing and processing 81 , 82 . Future characterization of SPOC domains from different proteins and species will address some key questions: is the SPOC domain a universal phospho-serine recognition module, how is the choice of binding partners determined, and how exactly do they regulate gene expression to ensure proper differentiation.…”

“…Yeast genetic studies have previously suggested competition between the yeast homolog Bye1 and Dst1 (TFIIS) for Pol II binding 32 , 34 but this model has never been experimentally tested. Using in vitro reconstitution, we showed that PHF3 competes with TFIIS for binding to Pol II and thereby impedes the rescue of backtracked Pol II.…”

“…The PHD-finger protein 3 (PHF3) belongs to a family of putative transcriptional regulators that includes the human Death-Inducer Obliterator (DIDO) and yeast Bypass of Ess-1 (Bye1) 31 , 32 . This family of proteins contains two motifs found in several transcription factors: a domain that is distantly related to the Pol II–associated domain of the elongation factor TFIIS, called the TFIIS-Like Domain (TLD), and a Plant Homeo Domain (PHD) 31 .…”

The Structure of theCandida albicansEss1 Prolyl Isomerase Reveals a Well-Ordered Linker that Restricts Domain Mobility,

“…Ess1 was originally identified in Saccharomyces cerevisiae , where it was shown to be essential for cell growth (), and later demonstrated to be a PPIase ( , ). In S. cerevisiae , Ess1 (ScEss1) binds the carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II ( , ) and controls multiple stages of transcription, including initiation and elongation ( , ). Ess1 orthologs have been identified in nearly all eukaryotic organisms that have been examined, including flies, humans, and other pathogenic fungi ( − ).…”

“…(CTD) of the large subunit of RNA polymerase II (21,22) and controls multiple stages of transcription, including initiation and elongation (23,24). Ess1 orthologs have been identified in nearly all eukaryotic organisms that have been examined, including flies, humans, and other pathogenic fungi (25)(26)(27)(28)(29).…”