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Inactivation of fission yeast Erh1 de-represses pho1 expression: evidence that Erh1 is a negative regulator of prt lncRNA termination.

TitleInactivation of fission yeast Erh1 de-represses pho1 expression: evidence that Erh1 is a negative regulator of prt lncRNA termination.
Publication TypeJournal Article
Year of Publication2020
AuthorsSchwer B, Sanchez AM, Shuman S
JournalRNA
Volume26
Issue10
Pagination1334-1344
Date Published2020 10
ISSN1469-9001
KeywordsAcid Phosphatase, Carrier Proteins, Gene Expression Regulation, Fungal, Inositol Phosphates, Promoter Regions, Genetic, RNA Polymerase II, RNA, Long Noncoding, RNA, Messenger, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Transcription Termination, Genetic
Abstract

Fission yeast Erh1 exists in a complex with RNA-binding protein Mmi1. Deletion of erh1 up-regulates the phosphate homeostasis gene pho1, which is normally repressed by transcription in cis of a 5' flanking prt lncRNA. Here we present evidence that de-repression of pho1 by erh1Δ is achieved through precocious 3'-processing/termination of prt lncRNA synthesis, to wit: (i) erh1Δ does not affect the activity of the prt or pho1 promoters per se; (ii) de-repression by erh1Δ depends on CPF (cleavage and polyadenylation factor) subunits Ctf1, Dis2, Ssu72, Swd22, and Ppn1 and on termination factor Rhn1; (iii) de-repression requires synthesis by the Asp1 IPP kinase of inositol 1-pyrophosphates (1-IPPs); (iv) de-repression is effaced by mutating Thr4 of the RNA polymerase II CTD to alanine; and (v) erh1Δ exerts an additive effect on pho1 de-repression in combination with mutating CTD Ser7 to alanine and with deletion of the IPP pyrophosphatase Aps1. These findings point to Erh1 as an antagonist of lncRNA termination in the prt-pho1 axis. In contrast, in mmi1Δ cells there is a reduction in pho1 mRNA and increase in the formation of a prt-pho1 read-through transcript, consistent with Mmi1 being an agonist of prt termination. We envision that Erh1 acts as a brake on Mmi1's ability to promote CPF-dependent termination during prt lncRNA synthesis. Consistent with this idea, erh1Δ de-repression of pho1 was eliminated by mutating the Mmi1-binding sites in the prt lncRNA.

DOI10.1261/rna.076463.120
Alternate JournalRNA
PubMed ID32546512
PubMed Central IDPMC7491324
Grant ListR01 GM052470 / GM / NIGMS NIH HHS / United States
R01 GM134021 / GM / NIGMS NIH HHS / United States
R35 GM126945 / GM / NIGMS NIH HHS / United States

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