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RNA polymerase II CTD interactome with 3' processing and termination factors in fission yeast and its impact on phosphate homeostasis.

TitleRNA polymerase II CTD interactome with 3' processing and termination factors in fission yeast and its impact on phosphate homeostasis.
Publication TypeJournal Article
Year of Publication2018
AuthorsSanchez AM, Shuman S, Schwer B
JournalProc Natl Acad Sci U S A
Volume115
Issue45
PaginationE10652-E10661
Date Published2018 11 06
ISSN1091-6490
KeywordsHomeostasis, Mutation, Peptide Termination Factors, Phosphates, Protein Domains, RNA Polymerase I, Schizosaccharomyces, Signal Transduction
Abstract

The carboxy-terminal domain (CTD) code encrypted within the YSPTSPS heptad repeats of RNA polymerase II (Pol2) is deeply rooted in eukaryal biology. Key steps to deciphering the code are identifying the events in gene expression that are governed by individual "letters" and then defining a vocabulary of multiletter "words" and their meaning. Thr4 and Ser7 exert opposite effects on the fission yeast gene, expression of which is repressed under phosphate-replete conditions by transcription of an upstream flanking long noncoding RNA (lncRNA). Here we attribute the derepression of by a CTD mutation to precocious termination of lncRNA synthesis, an effect that is erased by mutations of cleavage-polyadenylation factor (CPF) subunits Ctf1, Ssu72, Ppn1, Swd22, and Dis2 and termination factor Rhn1. By contrast, a CTD mutation hyperrepresses , as do CPF subunit and Rhn1 mutations, implying that reduces lncRNA termination. Moreover, CTD is synthetically lethal with ∆ and ∆, signifying that Thr4 and the Ppn1•Swd22 module play important, functionally redundant roles in promoting Pol2 termination. We find that Ppn1 and Swd22 become essential for viability when the CTD array is curtailed and that overcomes the need for Ppn1•Swd22 in the short CTD context. Mutational synergies highlight redundant essential functions of () Ppn1•Swd22 and Rhn1, () Ppn1•Swd22 and Ctf1, and () Ssu72 and Dis2 phosphatases. CTD alleles , , and have overlapping synthetic lethalities with ∆ and ∆, suggesting that Tyr1-Ser2-Thr4 form a three-letter CTD word that abets termination, with Rhn1 being a likely "reader" of this word.

DOI10.1073/pnas.1810711115
Alternate JournalProc Natl Acad Sci U S A
PubMed ID30355770
PubMed Central IDPMC6233144
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
R01 GM052470 / GM / NIGMS NIH HHS / United States
R35 GM126945 / GM / NIGMS NIH HHS / United States

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