Genetic screen for suppression of transcriptional interference reveals fission yeast 14-3-3 protein Rad24 as an antagonist of precocious Pol2 transcription termination Journal Article

   

Authors:	Garg, A.; Shuman, S.; Schwer, B.
Article Title:	Genetic screen for suppression of transcriptional interference reveals fission yeast 14-3-3 protein Rad24 as an antagonist of precocious Pol2 transcription termination
Abstract:	Expression of fission yeast Pho1 acid phosphatase is repressed under phosphate-replete conditions by transcription of an upstream prt lncRNA that interferes with the pho1 mRNA promoter. lncRNA control of pho1 mRNA synthesis is influenced by inositol pyrophosphate (IPP) kinase Asp1, deletion of which results in pho1 hyper-repression. A forward genetic screen for ADS (Asp1 Deletion Suppressor) mutations identified the 14-3-3 protein Rad24 as a governor of phosphate homeostasis. Production of full-length interfering prt lncRNA was squelched in rad24Δ cells, concomitant with increased production of pho1 mRNA and increased Pho1 activity, while shorter precociously terminated non-interfering prt transcripts persisted. Epistasis analysis showed that pho1 de-repression by rad24Δ depends on: (i) 3'-processing and transcription termination factors CPF, Pin1, and Rhn1; and (ii) Threonine-4 of the Pol2 CTD. Combining rad24Δ with the IPP pyrophosphatase-dead asp1-H397A allele caused a severe synthetic growth defect that was ameliorated by loss-of-function mutations in CPF, Pin1, and Rhn1, and by CTD phospho-site mutations T4A and Y1F. Rad24 function in repressing pho1 was effaced by mutation of its phosphate-binding pocket. Our findings instate a new role for a 14-3-3 protein as an antagonist of precocious RNA 3'-processing/termination. © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
Keywords:	gene deletion; genetics; mutation; sequence deletion; cell cycle protein; metabolism; cell cycle proteins; gene expression profiling; rna interference; genetic transcription; transcription, genetic; structure activity relation; structure-activity relationship; gene expression regulation; chemistry; amino acid sequence; signal peptide; intracellular signaling peptides and proteins; models, molecular; protein subunit; protein subunits; rna polymerase ii; mutagenesis; molecular model; gene expression regulation, fungal; schizosaccharomyces; schizosaccharomyces pombe proteins; 14-3-3 proteins; chromosome mapping; schizosaccharomyces pombe protein; acid phosphatase; transcription termination; protein 14 3 3; whole genome sequencing; long untranslated rna; chromosomal mapping; rna, long noncoding; rad24 protein, s pombe; lethal mutation; synthetic lethal mutations; transcription termination, genetic
Journal Title:	Nucleic Acids Research
Volume:	50
Issue:	2
ISSN:	0305-1048
Publisher:	Oxford University Press
Date Published:	2022-01-25
Start Page:	803
End Page:	819
Language:	English
DOI:	10.1093/nar/gkab1263
PUBMED:	34967420
PROVIDER:	scopus
PMCID:	PMC8789043
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85123878766&doi=10.1093%2fnar%2fgkab1263&partnerID=40&md5=fb7b51b61818fae1eac3cccd75944758
Notes:	Article -- Export Date: 1 March 2022 -- Source: Scopus

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