Yeast Nrd1, Nab3, and Sen1 transcriptome-wide binding maps suggest multiple roles in post-transcriptional RNA processing

Jamonnak, Nuttara; Creamer, Tyler J.; Darby, Miranda M.; Schaughency, Paul; Wheelan, Sarah J.; Corden, Jeffry L.

doi:10.1261/rna.2840711

Cited by 88 publications

(119 citation statements)

References 67 publications

(107 reference statements)

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“…To control for effects of the tag, we carried out PAR-CLIP on the FRB-tagged strain with or without rapamycin and a control strain that does not contain an FRB tag but does include the downstream HIS3 marker that was used to introduce the tag. We also conducted PAR-CLIP on an NAB3-HTB strain to map Nab3 binding sites on nascent RNA transcripts (15,41,42). PAR-CLIP data sets were obtained from two biological replicates for each of these conditions.…”

Section: Resultsmentioning

confidence: 99%

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Yeast RNA-Binding Protein Nab3 Regulates Genes Involved in Nitrogen Metabolism

Merran

Corden

2017

Molecular and Cellular Biology

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Termination of Saccharomyces cerevisiae RNA polymerase II (Pol II) transcripts occurs through two alternative pathways. Termination of mRNAs is coupled to cleavage and polyadenylation while noncoding transcripts are terminated through the Nrd1-Nab3-Sen1 (NNS) pathway in a process that is linked to RNA degradation by the nuclear exosome. Some mRNA transcripts are also attenuated through premature termination directed by the NNS complex. In this paper we present the results of nuclear depletion of the NNS component Nab3. As expected, many noncoding RNAs fail to terminate properly. In addition, we observe that nitrogen catabolite-repressed genes are upregulated by Nab3 depletion.KEYWORDS nitrogen metabolism, noncoding RNA, termination, transcription S accharomyces cerevisiae RNA polymerase II (Pol II) synthesizes both mRNAs and noncoding RNAs (ncRNAs), including snRNAs, snoRNAs, and a large number of RNAs with unknown functions (1, 2). The latter class includes cryptic unstable transcripts (CUTs) and stable uncharacterized transcripts (SUTs) (3, 4). Both coding and noncoding transcripts originate from promoters located in nucleosome-free regions in a process that requires both general transcription factors and gene-specific factors (5-7), but termination of these different classes of Pol II transcripts takes place through two different processes. Stable transcripts like mRNA and SUTs terminate through a process linked to cleavage and polyadenylation while snoRNAs and CUTs terminate through the Nrd1-Nab3-Sen1 (NNS) pathway (8)(9)(10)(11)(12)(13)(14).The NNS complex contains two RNA-binding proteins, Nrd1 and Nab3, which recognize specific sequences in nascent transcripts and direct termination in a process that requires the RNA helicase Sen1 (8,9,(15)(16)(17)(18)(19)(20). NNS interacts with Pol II in part through binding of Nrd1 to phosphorylated Ser5 on the C-terminal domain (CTD) (21-23), a pattern of CTD phosphorylation most prominent in the early stages of the transcription cycle, limiting NNS termination to promoter-proximal transcripts (24-29). The NNS complex also interacts with the TRAMP (Trf4/Trf5-Air1/Air2-Mtr4 polyadenylation) complex to couple termination to processing by the nuclear exosome (30)(31)(32)(33).While the two yeast Pol II termination pathways generally operate on distinct sets of transcripts, there are some genes that can use either termination pathway (11). In some cases NNS acts downstream of genes as a fail-safe termination mechanism to ensure that transcripts that fail to terminate through the cleavage/polyadenylation mechanism do not read through into downstream genes (34,35). In other cases NNS functions upstream to terminate transcripts before the poly(A) site is reached. For example, Nrd1 autoregulates its own transcription by binding, along with Nab3, to sites in the 5= end of its nascent pre-mRNA (9, 36). The result of this binding leads to premature termination of the majority of Nrd1 transcripts close to the 5= end. Nrd1 transcripts that escape the NNS pathway go on to t...

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Section: Resultsmentioning

confidence: 99%

“…Nrd1 mutants are synthetic lethal, with mutations that activate the Ras-protein kinase A (PKA) signaling pathway, and the pattern of Nrd1 binding changes upon glucose deprivation (42). Recent studies have shown that Nab3 is also important in reshaping the transcriptome in response to glucose deprivation (45,55).…”

Section: Discussionmentioning

confidence: 99%

Yeast RNA-Binding Protein Nab3 Regulates Genes Involved in Nitrogen Metabolism

Merran

Corden

2017

Molecular and Cellular Biology

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“…The TRAMP (Trf4, Air2, Mtr4) complex then adds a short polyadenosine tail to the 39 end (Fig. 3), which is ultimately removed by the nuclear exosome (Jamonnak et al 2011;Kuehner et al 2011).…”

Section: Yeast Telomerase Rnp Maturation and Tert-ter Assemblymentioning

confidence: 99%

Biogenesis of telomerase ribonucleoproteins

Egan

Collins

2012

RNA

153

168

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Telomerase adds simple-sequence repeats to the ends of linear chromosomes to counteract the loss of end sequence inherent in conventional DNA replication. Catalytic activity for repeat synthesis results from the cooperation of the telomerase reverse transcriptase protein (TERT) and the template-containing telomerase RNA (TER). TERs vary widely in sequence and structure but share a set of motifs required for TERT binding and catalytic activity. Species-specific TER motifs play essential roles in RNP biogenesis, stability, trafficking, and regulation. Remarkably, the biogenesis pathways that generate mature TER differ across eukaryotes. Furthermore, the cellular processes that direct the assembly of a biologically functional telomerase holoenzyme and its engagement with telomeres are evolutionarily varied and regulated. This review highlights the diversity of strategies for telomerase RNP biogenesis, RNP assembly, and telomere recruitment among ciliates, yeasts, and vertebrates and suggests common themes in these pathways and their regulation.

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“…Generation of the mature nonpolyadenylated 3 ′ -end occurs via the Nrd1-dependent noncoding RNA termination pathway (Jamonnak et al 2011;Noël et al 2012). The RNA has been proposed to fold into a distinct structure that may function as a central scaffolding element for the RNP (Dandjinou et al 2004;Zappulla and Cech 2004;Lebo and Zappulla 2012).…”

Section: Introductionmentioning

confidence: 99%

Cell cycle–dependent transcription factors control the expression of yeast telomerase RNA

Dionne

Larose

Dandjinou

et al. 2013

RNA

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Telomerase is a specialized ribonucleoprotein that adds repeated DNA sequences to the ends of eukaryotic chromosomes to preserve genome integrity. Some secondary structure features of the telomerase RNA are very well conserved, and it serves as a central scaffold for the binding of associated proteins. The Saccharomyces cerevisiae telomerase RNA, TLC1, is found in very low copy number in the cell and is the limiting component of the known telomerase holoenzyme constituents. The reasons for this low abundance are unclear, but given that the RNA is very stable, transcriptional control mechanisms must be extremely important. Here we define the sequences forming the TLC1 promoter and identify the elements required for its low expression level, including enhancer and repressor elements. Within an enhancer element, we found consensus sites for Mbp1/Swi4 association, and chromatin immunoprecipitation (ChIP) assays confirmed the binding of Mbp1 and Swi4 to these sites of the TLC1 promoter. Furthermore, the enhancer element conferred cell cycle-dependent regulation to a reporter gene, and mutations in the Mbp1/Swi4 binding sites affected the levels of telomerase RNA and telomere length. Finally, ChIP experiments using a TLC1 RNA-binding protein as target showed cell cycle-dependent transcription of the TLC1 gene. These results indicate that the budding yeast TLC1 RNA is transcribed in a cell cycle-dependent fashion late in G1 and may be part of the S phase-regulated group of genes involved in DNA replication.

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Yeast Nrd1, Nab3, and Sen1 transcriptome-wide binding maps suggest multiple roles in post-transcriptional RNA processing

Cited by 88 publications

References 67 publications

Yeast RNA-Binding Protein Nab3 Regulates Genes Involved in Nitrogen Metabolism

Yeast RNA-Binding Protein Nab3 Regulates Genes Involved in Nitrogen Metabolism

Biogenesis of telomerase ribonucleoproteins

Cell cycle–dependent transcription factors control the expression of yeast telomerase RNA

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