Transcriptomes of six mutants in the Sen1 pathway reveal combinatorial control of transcription termination across the Saccharomyces cerevisiae genome

Transcriptome studies on eukaryotic cells have revealed an unexpected abundance and diversity of noncoding RNAs synthesized by RNA polymerase II (Pol II), some of which influence the expression of protein-coding genes. Yet, much less is known about biogenesis of Pol II non-coding RNA than mRNAs. In the budding yeast Saccharomyces cerevisiae, initiation of non-coding transcripts by Pol II appears to be similar to that of mRNAs, but a distinct pathway is utilized for termination of most non-coding RNAs: the Sen1-dependent or “NNS” pathway. Here, we examine the effect on the S. cerevisiae transcriptome of conditional mutations in the genes encoding six different essential proteins that influence Sen1-dependent termination: Sen1, Nrd1, Nab3, Ssu72, Rpb11, and Hrp1. We observe surprisingly diverse effects on transcript abundance for the different proteins that cannot be explained simply by differing severity of the mutations. Rather, we infer from our results that termination of Pol II transcription of non-coding RNA genes is subject to complex combinatorial control that likely involves proteins beyond those studied here. Furthermore, we identify new targets and functions of Sen1-dependent termination, including a role in repression of meiotic genes in vegetative cells. In combination with other recent whole-genome studies on termination of non-coding RNAs, our results provide promising directions for further investigation.

• Publication year

  2017

• Venue

  PLoS Genetics

• Publication date

  2017-06-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pgen.1006863PMID 28665995PMCID 5513554
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Regulation of a Eukaryotic Gene by GTP-Dependent Start Site Selection and Transcription Attenuation.

  2019cited by this paper
• Sen1 has unique structural features grafted on the architecture of the Upf1‐like helicase family

  2017cited by this paper
• Common genomic elements promote transcriptional and DNA replication roadblocks

  2016cited by this paper
• Nab3 Facilitates the Function of the TRAMP Complex in RNA Processing via Recruitment of Rrp6 Independent of Nrd1

  2015cited by this paper
• The Exosome Component Rrp6 Is Required for RNA Polymerase II Termination at Specific Targets of the Nrd1-Nab3 Pathway

  2015cited by this paper
• Saccharomyces cerevisiae Sen1 Helicase Domain Exhibits 5′- to 3′-Helicase Activity with a Preference for Translocation on DNA Rather than RNA*♦

  2015cited by this paper
• Termination of Transcription of Short Noncoding RNAs by RNA Polymerase II.

  2015cited by this paper
• Role of histone modifications and early termination in pervasive transcription and antisense-mediated gene silencing in yeast

  2014cited by this paper
• Genome-wide identification of transcript start and end sites by transcript isoform sequencing

  2014cited by this paper
• The Ssu72 Phosphatase Mediates the RNA Polymerase II Initiation-Elongation Transition*

  2014cited by this paper
• Saccharomyces cerevisiae Sen1 as a Model for the Study of Mutations in Human Senataxin That Elicit Cerebellar Ataxia

  2014cited by this paper
• Structure and semi-sequence-specific RNA binding of Nrd1

  2014cited by this paper
• PAR-CLIP data indicate that Nrd1-Nab3-dependent transcription termination regulates expression of hundreds of protein coding genes in yeast

  2014cited by this paper
• Genome-Wide Mapping of Yeast RNA Polymerase II Termination

  2014cited by this paper
• The yeast Cyc 8-Tup 1 complex cooperates with Hda 1 p and Rpd 3 p histone deacetylases to robustly repress transcription of the subtelomeric FLO 1 gene

  2014cited by this paper
• The yeast Cyc8–Tup1 complex cooperates with Hda1p and Rpd3p histone deacetylases to robustly repress transcription of the subtelomeric FLO1 gene

  2014cited by this paper
• Transcriptome surveillance by selective termination of noncoding RNA synthesis.

  2013cited by this paper
• A Network of Interdependent Molecular Interactions Describes a Higher Order Nrd1-Nab3 Complex Involved in Yeast Transcription Termination*

  2013cited by this paper
• Extensive transcriptional heterogeneity revealed by isoform profiling

  2013cited by this paper
• Dealing with pervasive transcription.

  2013cited by this paper
• Nuclear RNA surveillance: role of TRAMP in controlling exosome specificity

  2013cited by this paper
• Gene regulation by antisense transcription

  2013cited by this paper
• A Transcriptome-wide Atlas of RNP Composition Reveals Diverse Classes of mRNAs and lncRNAs

  2013cited by this paper
• Interactions of Sen1, Nrd1, and Nab3 with Multiple Phosphorylated Forms of the Rpb1 C-Terminal Domain in Saccharomyces cerevisiae

  2012cited by this paper
• A genetic screen for terminator function in yeast identifies a role for a new functional domain in termination factor Nab3

  2012cited by this paper
• YeastMine—an integrated data warehouse for Saccharomyces cerevisiae data as a multipurpose tool-kit

  2012cited by this paper
• A universal RNA polymerase II CTD cycle is orchestrated by complex interplays between kinase, phosphatase, and isomerase enzymes along genes.

  2012cited by this paper
• Serine phosphorylation and proline isomerization in RNAP II CTD control recruitment of Nrd1.

  2012cited by this paper
• Transcription of two long noncoding RNAs mediates mating-type control of gametogenesis in budding yeast.

  2012cited by this paper
• The Saccharomyces cerevisiae Nrd1-Nab3 Transcription Termination Pathway Acts in Opposition to Ras Signaling and Mediates Response to Nutrient Depletion

  2012cited by this paper
• Ssu72 Phosphatase-dependent Erasure of Phospho-Ser7 Marks on the RNA Polymerase II C-terminal Domain Is Essential for Viability and Transcription Termination*

  2012cited by this paper
• Rhn1, a Nuclear Protein, Is Required for Suppression of Meiotic mRNAs in Mitotically Dividing Fission Yeast

  2012cited by this paper
• Intergenic transcription causes repression by directing nucleosome assembly.

  2011cited by this paper
• Regulated Antisense Transcription Controls Expression of Cell-Type-Specific Genes in Yeast

  2011cited by this paper
• Crystal structure of Ssu72, an essential eukaryotic phosphatase specific for the C-terminal domain of RNA polymerase II, in complex with a transition state analogue.

  2011cited by this paper
• High-Resolution View of the Yeast Meiotic Program Revealed by Ribosome Profiling

  2011cited by this paper
• Mpk1 MAPK association with the Paf1 complex blocks Sen1-mediated premature transcription termination.

  2011cited by this paper
• Yeast Nrd1, Nab3, and Sen1 transcriptome-wide binding maps suggest multiple roles in post-transcriptional RNA processing.

  2011cited by this paper
• The nuclear RNA polymerase II surveillance system targets polymerase III transcripts

  2011cited by this paper
• Transcriptome-Wide Binding Sites for Components of the Saccharomyces cerevisiae Non-Poly(A) Termination Pathway: Nrd1, Nab3, and Sen1

  2011cited by this paper
• Unravelling the means to an end: RNA polymerase II transcription termination

  2011cited by this paper
• RNA synthesis precision is regulated by preinitiation complex turnover.

  2010cited by this paper
• Execution of the meiotic noncoding RNA expression program and the onset of gametogenesis in yeast require the conserved exosome subunit Rrp6

  2010cited by this paper
• Comprehensive polyadenylation site maps in yeast and human reveal pervasive alternative polyadenylation.

  2010cited by this paper
• Structural insights into cis element recognition of non-polyadenylated RNAs by the Nab3-RRM

  2010cited by this paper
• Bidirectional promoters generate pervasive transcription in yeast

  2009cited by this paper
• Widespread bidirectional promoters are the major source of cryptic transcripts in yeast

  2009cited by this paper
• Transcription termination by nuclear RNA polymerases.

  2009cited by this paper
• Fail-Safe Transcriptional Termination for Protein-Coding Genes in S. cerevisiae

  2009cited by this paper
• Yeast RNase III triggers polyadenylation-independent transcription termination.

  2009cited by this paper
• The Integrated Genome Browser: free software for distribution and exploration of genome-scale datasets

  2009cited by this paper
• Phosphorylation of the RNA polymerase II C-terminal domain dictates transcription termination choice

  2008cited by this paper
• Properties of an Intergenic Terminator and Start Site Switch That Regulate IMD2 Transcription in Yeast

  2008cited by this paper
• Mutations of RNA polymerase II activate key genes of the nucleoside triphosphate biosynthetic pathways

  2008cited by this paper
• The Nrd1–Nab3–Sen1 termination complex interacts with the Ser5-phosphorylated RNA polymerase II C-terminal domain

  2008cited by this paper
• Regulation of a eukaryotic gene by GTP-dependent start site selection and transcription attenuation.

  2008cited by this paper
• Futile cycle of transcription initiation and termination modulates the response to nucleotide shortage in S. cerevisiae.

  2008cited by this paper
• Interaction of yeast RNA-binding proteins Nrd1 and Nab3 with RNA polymerase II terminator elements.

  2007cited by this paper
• cis- and trans-Acting Determinants of Transcription Termination by Yeast RNA Polymerase II

  2006cited by this paper
• Genome-wide distribution of yeast RNA polymerase II and its control by Sen1 helicase.

  2006cited by this paper
• Cytoplasmic Decay of Intergenic Transcripts in Saccharomyces cerevisiae

  2006cited by this paper
• Regulation of yeast NRD1 expression by premature transcription termination.

  2006cited by this paper
• in Saccharomyces cerevisiae

  2005cited by this paper
• Recognition of RNA polymerase II carboxy-terminal domain by 3′-RNA-processing factors

  2004cited by this paper
• Identification of cis Elements Directing Termination of Yeast Nonpolyadenylated snoRNA Transcripts

  2004cited by this paper
• Ssu72 Is an RNA polymerase II CTD phosphatase.

  2004cited by this paper
• Complete RNA polymerase II elongation complex structure and its interactions with NTP and TFIIS.

  2004cited by this paper
• Multiple protein/protein and protein/RNA interactions suggest roles for yeast DNA/RNA helicase Sen1p in transcription, transcription-coupled DNA repair and RNA processing.

  2004cited by this paper
• Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene

  2004cited by this paper
• Functional interactions between the transcription and mRNA 3' end processing machineries mediated by Ssu72 and Sub1.

  2003cited by this paper
• Organization and Function of APT, a Subcomplex of the Yeast Cleavage and Polyadenylation Factor Involved in the Formation of mRNA and Small Nucleolar RNA 3′-Ends*

  2003cited by this paper
• Ssu72 Protein Mediates Both Poly(A)-Coupled and Poly(A)-Independent Termination of RNA Polymerase II Transcription

  2003cited by this paper
• Ssu72 is a phosphatase essential for transcription termination of snoRNAs and specific mRNAs in yeast

  2003cited by this paper
• RNA-binding protein Nrd1 directs poly(A)-independent 3′-end formation of RNA polymerase II transcripts

  2001cited by this paper
• Expression of the yeast glycogen phosphorylase gene is regulated by stress‐response elements and by the HOG MAP kinase pathway

  2001cited by this paper
• Precursors to the U3 Small Nucleolar RNA Lack Small Nucleolar RNP Proteins but Are Stabilized by La Binding

  2000cited by this paper
• A yeast heterogeneous nuclear ribonucleoprotein complex associated with RNA polymerase II.

  2000cited by this paper
• U1 snRNA is cleaved by RNase III and processed through an Sm site-dependent pathway.

  1999cited by this paper
• Yeast RNase III as a key processing enzyme in small nucleolar RNAs metabolism.

  1998cited by this paper
• Depletion of yeast RNase III blocks correct U2 3′ end formation and results in polyadenylated but functional U2 snRNA

  1998cited by this paper
• Control of pre-mRNA accumulation by the essential yeast protein Nrd1 requires high-affinity transcript binding and a domain implicated in RNA polymerase II association.

  1998cited by this paper
• Alternative 3'-end processing of U5 snRNA by RNase III.

  1997cited by this paper
• Hrp1, a sequence-specific RNA-binding protein that shuttles between the nucleus and the cytoplasm, is required for mRNA 3'-end formation in yeast.

  1997cited by this paper
• Repression of gene expression by an exogenous sequence element acting in concert with a heterogeneous nuclear ribonucleoprotein-like protein, Nrd1, and the putative helicase Sen1

  1996cited by this paper
• The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins.

  1996cited by this paper
• A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae.

  1990cited by this paper
• Molecular analysis of GPH1, the gene encoding glycogen phosphorylase in Saccharomyces cerevisiae

  1989cited by this paper
• Nab 3 Facilitates the Function of the TRAMP Complex in RNA Processing via Recruitment of Rrp 6 Independent of Nrd 1

  year unknowncited by this paper

• Direct RNA-seq provides evidence for an antiterminator function of the yeast Hrp1 protein on RNA polymerase II transcripts

  2025influential citation
• Substitutions in RNA-binding protein Hrp1 map a potential interaction surface with the yeast RNA polymerase II elongation complex.

  2025cites this paper
• The functionality of telomerase depends on CPF–CF induced 3′end processing of its RNA component TLC1 and a novel Nrd1–Nab3 surveillance mechanism

  2025cites this paper
• Substitutions in RNA-binding protein Hrp1 map a potential interaction surface with the yeast RNA polymerase II elongation complex

  2025cites this paper
• A transcription termination mechanism for maintaining homogeneous protein expression

  2025cites this paper
• Domains and residues of the Saccharomyces cerevisiae hnRNP protein Hrp1 important for transcriptional autoregulation and noncoding RNA termination.

  2023cites this paper
• Mutations in yeast Pcf11, a conserved protein essential for mRNA 3' end processing and transcription termination, elicit the Environmental Stress Response.

  2023cites this paper
• CTP sensing and Mec1ATR-Rad53CHK1/CHK2 mediate a two-layered response to inhibition of glutamine metabolism

  2022cites this paper
• RNA polymerase II transcription attenuation at the yeast DNA repair gene DEF1 is biologically significant and dependent on the Hrp1 RNA-recognition motif

  2022cites this paper
• RNA Polymerase II CTD phosphatase Rtr1 fine-tunes transcription termination

  2020cites this paper
• Natural population re-sequencing detects the genetic basis of local adaptation to low temperature in a woody plant

  2020cites this paper
• Charcot-Marie-Tooth disease

  2019cites this paper
• Perturbation of mRNP biogenesis reveals a dynamic landscape of the Rrp6-dependent surveillance machinery trafficking along the yeast genome

  2019cites this paper
• Flocculation of Saccharomyces cerevisiae is dependent on activation of Slt2 and Rlm1 regulated by the cell wall integrity pathway

  2019influential citation
• Diverse roles of Tup1p and Cyc8p transcription regulators in the development of distinct types of yeast populations

  2018cites this paper
• A novel link between Cell Wall Integrity pathway and Flocculation, regulated by yeast Sen1 dependent interplay between Rlm1 and Tup1

  2018influential citation
• The DEAD-box protein Dbp2p is linked to noncoding RNAs, the helicase Sen1p, and R-loops

  2018cites this paper
• Termination of non-coding transcription in yeast relies on both a CTD-interaction domain and a CTD-mimic in Sen1

  2018cites this paper
• Nuclear fate of yeast snoRNA is determined by co-transcriptional Rnt1 cleavage

  2018cites this paper
• RNA Polymerase II Transcription Attenuation at the Yeast DNA Repair Gene, DEF1, Involves Sen1-Dependent and Polyadenylation Site-Dependent Termination

  2018cites this paper
• The hnRNP-like Nab3 termination factor can employ heterologous prion-like domains in place of its own essential low complexity domain

  2017cites this paper