How an mRNA capping enzyme reads distinct RNA polymerase II and Spt5 CTD phosphorylation codes Journal Article
| Authors: | Doamekpor, S. K.; Sanchez, A. M.; Schwer, B.; Shuman, S.; Lima, C. D. |
| Article Title: | How an mRNA capping enzyme reads distinct RNA polymerase II and Spt5 CTD phosphorylation codes |
| Abstract: | Interactions between RNA guanylyltransferase (GTase) and the C-terminal domain (CTD) repeats of RNA polymerase II (Pol2) and elongation factor Spt5 are thought to orchestrate cotranscriptional capping of nascent mRNAs. The crystal structure of a fission yeast GTase«Pol2 CTD complex reveals a unique docking site on the nucleotidyl transferase domain for an 8-amino-acid Pol2 CTD segment, S5PPSYSPTS5P, bracketed by two Ser5-PO4 marks. Analysis of GTase mutations that disrupt the Pol2 CTD interface shows that at least one of the two Ser5-PO4-binding sites is required for cell viability and that each site is important for cell growth at 37°C. Fission yeast GTase binds the Spt5 CTD at a separate docking site in the OB-fold domain that captures the Trp4 residue of the Spt5 nonapeptide repeat T1PAW4NSGSK. A disruptive mutation in the Spt5 CTD-binding site of GTase is synthetically lethal with mutations in the Pol2 CTD-binding site, signifying that the Spt5 and Pol2 CTDs cooperate to recruit capping enzyme in vivo. CTD phosphorylation has opposite effects on the interaction of GTase with Pol2 (Ser5-PO4 is required for binding) versus Spt5 (Thr1-PO4 inhibits binding). We propose that the state of Thr1 phosphorylation comprises a binary "Spt5 CTD code" that is read by capping enzyme independent of and parallel to its response to the state of the Pol2 CTD. © 2014 Doamekpor et al. |
| Keywords: | transcription; regulation; rna polymerase ii; mrna capping; spt5 |
| Journal Title: | Genes and Development |
| Volume: | 28 |
| Issue: | 12 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2014-01-01 |
| Start Page: | 1323 |
| End Page: | 1336 |
| Language: | English |
| DOI: | 10.1101/gad.242768.114 |
| PROVIDER: | scopus |
| PMCID: | PMC4066402 |
| PUBMED: | 24939935 |
| DOI/URL: | |
| Notes: | Genes Dev. -- Export Date: 8 July 2014 -- CODEN: GEDEE -- Source: Scopus |
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