Duf89 abets lncRNA control of fission yeast phosphate homeostasis via its antagonism of precocious lncRNA transcription termination Journal Article

   

Authors:	Sanchez, A. M.; Garg, A.; Schwer, B.; Shuman, S.
Article Title:	Duf89 abets lncRNA control of fission yeast phosphate homeostasis via its antagonism of precocious lncRNA transcription termination
Abstract:	Fission yeast phosphate homeostasis gene pho1 is actively repressed during growth in phosphate-rich medium by transcription in cis of a long noncoding (lnc) RNA from the 5' flanking prt(nc-pho1) gene. Pho1 expression is: (i) derepressed by genetic maneuvers that favor precocious lncRNA 3'-processing and termination, in response to DSR and PAS signals in prt; and (ii) hyperrepressed in genetic backgrounds that dampen 3'-processing/termination efficiency. Governors of 3'-processing/termination include the RNA polymerase CTD code, the CPF (cleavage and polyadenylation factor) complex, termination factors Seb1 and Rhn1, and the inositol pyrophosphate signaling molecule 1,5-IP8 Here, we present genetic and biochemical evidence that fission yeast Duf89, a metal-dependent phosphatase/pyrophosphatase, is an antagonist of precocious 3'-processing/termination. We show that derepression of pho1 in duf89Δ cells correlates with squelching the production of full-length prt lncRNA and is erased or attenuated by: (i) DSR/PAS mutations in prt; (ii) loss-of-function mutations in components of the 3'-processing and termination machinery; (iii) elimination of the CTD Thr4-PO4 mark; (iv) interdicting CTD prolyl isomerization by Pin1; (v) inactivating the Asp1 kinase that synthesizes IP8; and (vi) loss of the putative IP8 sensor Spx1. The findings that duf89Δ is synthetically lethal with pho1-derepressive mutations CTD-S7A and aps1Δ-and that this lethality is rescued by CTD-T4A, CPF/Rhn1/Pin1 mutations, and spx1Δ-implicate Duf89 more broadly as a collaborator in cotranscriptional regulation of essential fission yeast genes. The duf89-D252A mutation, which abolishes Duf89 phosphohydrolase activity, phenocopied duf89+, signifying that duf89Δ phenotypes are a consequence of Duf89 protein absence, not absence of Duf89 catalysis. © 2023 Sanchez et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
Keywords:	genetics; metabolism; genetic transcription; transcription, genetic; homeostasis; phosphate; phosphates; rna polymerase ii; schizosaccharomyces; schizosaccharomyces pombe proteins; schizosaccharomyces pombe protein; schizosaccharomyces pombe; transcription termination; long untranslated rna; rna, long noncoding; transcription termination, genetic; cleavage and polyadenylation factor; inositol pyrophosphate dynamics; pol2 ctd code
Journal Title:	RNA
Volume:	29
Issue:	6
ISSN:	1355-8382
Publisher:	Cold Spring Harbor Laboratory Press
Date Published:	2023-06-01
Start Page:	808
End Page:	825
Language:	English
DOI:	10.1261/rna.079595.123
PUBMED:	36882296
PROVIDER:	scopus
PMCID:	PMC10187668
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85159741679&doi=10.1261%2frna.079595.123&partnerID=40&md5=5ccc989bbf8fc09fa7d466906f05cf48
Notes:	Article -- Export Date: 1 June 2023 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/206575