气候变化领域集成服务门户(CCPortal): Genetic screen for suppression of transcriptional interference identifies a gain-of-function mutation in Pol2 termination factor Seb1

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DOI	10.1073/pnas.2108105118
	Genetic screen for suppression of transcriptional interference identifies a gain-of-function mutation in Pol2 termination factor Seb1
	Schwer B.; Garg A.; Jacewicz A.; Shuman S.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:33
英文摘要	The system of long noncoding RNA (lncRNA)-mediated transcriptional interference that represses fission yeast phosphate homoeostasis gene pho1 provides a sensitive readout of genetic influences on cotranscriptional 3′-processing and termination and a tool for discovery of regulators of this phase of the Pol2 transcription cycle. Here, we conducted a genetic screen for relief of transcriptional interference that unveiled a mechanism by which Pol2 termination is enhanced via a gain-of-function mutation, G476S, in the RNA-binding domain of an essential termination factor, Seb1. The genetic and physical evidence for gain-of-function is compelling: 1) seb1-G476S de-represses pho1 and tgp1, both of which are subject to lncRNA-mediated transcriptional interference; 2) seb1-G476S elicits precocious lncRNA transcription termination in response to lncRNA 5′-proximal poly(A) signals; 3) seb1-G476S derepression of pho1 is effaced by loss-of-function mutations in cleavage and polyadenylation factor (CPF) subunits and termination factor Rhn1; 4) synthetic lethality of seb1-G476S with pho1 derepressive mutants rpb1-CTD-S7A and aps1Δ is rescued by CPF/Rhn1 loss-of-function alleles; and 5) seb1-G476S elicits an upstream shift in poly(A) site preference in several messenger RNA genes. A crystal structure of the Seb1-G476S RNA-binding domain indicates potential for gain of contacts from Ser476 to RNA nucleobases. To our knowledge, this is a unique instance of a gain-of-function phenotype in a eukaryal transcription termination protein. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CTD code; Inositol pyrophosphates; Phosphate homeostasis; RNA 3′-processing; Transcription termination
语种	英语
scopus关键词	cleavage and polyadenylation specificity factor; inositol; long untranslated RNA; messenger RNA; nucleic acid base; pyrophosphate; RNA polymerase II; termination factor Rhn1; translation termination factor; translation termination factor Seb1; unclassified drug; fungal protein; long untranslated RNA; pyrophosphate; aps1 gene; Article; controlled study; CPF gene; crystal structure; G476S gene; gain of function mutation; gene; genetic screening; loss of function mutation; nonhuman; phenotype; pho1 gene; phosphate metabolism; Rhn1 gene; RNA interference; RNA-binding domain; rpb1-CTD-S7A gene; tgp1 gene; transcriptional interference; cell survival; gene expression regulation; genetics; metabolism; physiology; protein subunit; Schizosaccharomyces; transcription termination; Cell Survival; Diphosphates; Fungal Proteins; Gain of Function Mutation; Gene Expression Regulation, Fungal; Protein Subunits; RNA, Long Noncoding; Schizosaccharomyces; Transcription Termination, Genetic
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251050
作者单位	Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States; Molecular Biology Program, Sloan Kettering Institute, New York, NY 10065, United States
推荐引用方式 GB/T 7714	Schwer B.,Garg A.,Jacewicz A.,et al. Genetic screen for suppression of transcriptional interference identifies a gain-of-function mutation in Pol2 termination factor Seb1[J],2021,118(33).
APA	Schwer B.,Garg A.,Jacewicz A.,&Shuman S..(2021).Genetic screen for suppression of transcriptional interference identifies a gain-of-function mutation in Pol2 termination factor Seb1.Proceedings of the National Academy of Sciences of the United States of America,118(33).
MLA	Schwer B.,et al."Genetic screen for suppression of transcriptional interference identifies a gain-of-function mutation in Pol2 termination factor Seb1".Proceedings of the National Academy of Sciences of the United States of America 118.33(2021).