Inositol pyrophosphates impact phosphate homeostasis via modulation of RNA 3' processing and transcription termination Journal Article

   


Authors: Sanchez, A. M.; Garg, A.; Shuman, S.; Schwer, B.
Article Title: Inositol pyrophosphates impact phosphate homeostasis via modulation of RNA 3' processing and transcription termination
Abstract: Fission yeast phosphate acquisition genes pho1, pho84, and tgp1 are repressed in phosphate-rich medium by transcription of upstream lncRNAs. Here, we show that phosphate homeostasis is subject to metabolite control by inositol pyrophosphates (IPPs), exerted through the 3'-processing/termination machinery and the Pol2 CTD code. Increasing IP8 (via Asp1 IPP pyrophosphatase mutation) de-represses the PHO regulon and leads to precocious termination of prt lncRNA synthesis. pho1 de-repression by IP8 depends on cleavage-polyadenylation factor (CPF) subunits, termination factor Rhn1, and the Thr4 letter of the CTD code. pho1 de-repression by mutation of the Ser7 CTD letter depends on IP8. Simultaneous inactivation of the Asp1 and Aps1 IPP pyrophosphatases is lethal, but this lethality is suppressed by mutations of CPF subunits Ppn1, Swd22, Ssu72, and Ctf1 and CTD mutation T4A. Failure to synthesize IP8 (via Asp1 IPP kinase mutation) results in pho1 hyper-repression. Synthetic lethality of asp1Δ with Ppn1, Swd22, and Ssu72 mutations argues that IP8 plays an important role in essential 3'-processing/termination events, albeit in a manner genetically redundant to CPF. Transcriptional profiling delineates an IPP-responsive regulon composed of genes overexpressed when IP8 levels are increased. Our results establish a novel role for IPPs in cell physiology. © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
Journal Title: Nucleic Acids Research
Volume: 47
Issue: 16
ISSN: 0305-1048
Publisher: Oxford University Press  
Date Published: 2019-09-19
Start Page: 8452
End Page: 8469
Language: English
DOI: 10.1093/nar/gkz567
PUBMED: 31276588
PROVIDER: scopus
PMCID: PMC6895273
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85073307738&doi=10.1093%2fnar%2fgkz567&partnerID=40&md5=f035fc2acad798dbd680346198d96b2b
Notes: Article -- Export Date: 1 November 2019 -- Source: Scopus
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MSK Authors
  1. Stewart H Shuman
    546 Shuman
  2. Angad Garg
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