Futile Cycle of Transcription Initiation and Termination Modulates the Response to Nucleotide Shortage in S. cerevisiae

Thiebaut, Marilyne; Colin, Jessie; Neil, Helen; Jacquier, Alain; Séraphin, Bertrand; Lacroute, François; Libri, Domenico

doi:10.1016/j.molcel.2008.08.010

Cited by 97 publications

(112 citation statements)

References 39 publications

(56 reference statements)

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…In our Nab3 anchor-away experiments, we confirm this result (Fig. 1A) and show that several genes involved in nucleotide biosynthesis that have previously been shown to be regulated by Nrd1 (37)(38)(39) are also upregulated by Nab3 depletion. Figure 1D shows that IMD2 and URA8 expression is increased when Nab3 is depleted from the nucleus.…”

Section: Resultssupporting

confidence: 88%

“…Nrd1 transcripts that escape the NNS pathway go on to terminate through the cleavage/ polyadenylation pathway, producing a mature mRNA. A similar form of regulation occurs with a number of genes encoding enzymes involved in nucleotide synthesis (37)(38)(39). In these cases, however, the use of alternative start sites leads to pre-mRNAs that have or do not have the Nrd1 and Nab3 binding sites in their 5= untranslated regions (UTRs) and therefore either terminate prematurely through NNS or elongate to produce a mature mRNA.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Merran

Corden

2017

Molecular and Cellular Biology

View full text Add to dashboard Cite

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...

show abstract

Section: Resultssupporting

confidence: 88%

mentioning

confidence: 99%

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

Merran

Corden

2017

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…However, expression of URA2 is not Ppr1 dependent (Losson and Lacroute 1981;Kwapisz et al 2008), but is regulated by a novel mechanism recently described. This mechanism involves alternative transcription start sites that lead to the synthesis of small "cryptic unstable transcripts" (CUTs) (Thiebaut et al 2008) but also to a downstream T-rich region (Kwapisz et al 2008). "Nonproductive" transcription from the upstream sites downregulates expression of the URA2 mRNA while uracil deprivation activates selection of the functional URA2 mRNA start site by a mechanism that does not involve lower expression of the CUTs (Thiebaut et al 2008) (Figure 14).…”

Section: Regulation Of Pyrimidine Metabolismmentioning

confidence: 99%

Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

2012

View full text Add to dashboard Cite

Ever since the beginning of biochemical analysis, yeast has been a pioneering model for studying the regulation of eukaryotic metabolism. During the last three decades, the combination of powerful yeast genetics and genome-wide approaches has led to a more integrated view of metabolic regulation. Multiple layers of regulation, from suprapathway control to individual gene responses, have been discovered. Constitutive and dedicated systems that are critical in sensing of the intra- and extracellular environment have been identified, and there is a growing awareness of their involvement in the highly regulated intracellular compartmentalization of proteins and metabolites. This review focuses on recent developments in the field of amino acid, nucleotide, and phosphate metabolism and provides illustrative examples of how yeast cells combine a variety of mechanisms to achieve coordinated regulation of multiple metabolic pathways. Importantly, common schemes have emerged, which reveal mechanisms conserved among various pathways, such as those involved in metabolite sensing and transcriptional regulation by noncoding RNAs or by metabolic intermediates. Thanks to the remarkable sophistication offered by the yeast experimental system, a picture of the intimate connections between the metabolomic and the transcriptome is becoming clear.

show abstract

“…For instance, binding of Nrd1 and Nab3 to the 59-UTR and upstream coding region of NRD1 directs premature termination, resulting in negative autoregulation of Nrd1 levels (Steinmetz et al 2001;Arigo et al 2006a). Likewise, termination of CUTs initiated upstream of the IMD2 mRNA start site regulates IMD2 mRNA expression (Jenks et al 2008;Kuehner and Brow 2008;Thiebaut et al 2008). All three attenuators are sensitive to mutations in SEN1 and RPB11, consistent with previous studies showing the importance of the Rpb3/11 heterodimer in termination (Steinmetz et al 2006a).…”

Section: A Wider Role For the Nrd1 Complex In Gene Expressionmentioning

confidence: 99%

Transcription termination by nuclear RNA polymerases

Richard

Manley²

2009

Genes Dev.

291

326

View full text Add to dashboard Cite

Gene transcription in the cell nucleus is a complex and highly regulated process. Transcription in eukaryotes requires three distinct RNA polymerases, each of which employs its own mechanisms for initiation, elongation, and termination. Termination mechanisms vary considerably, ranging from relatively simple to exceptionally complex. In this review, we describe the present state of knowledge on how each of the three RNA polymerases terminates and how mechanisms are conserved, or vary, from yeast to human.

show abstract

Futile Cycle of Transcription Initiation and Termination Modulates the Response to Nucleotide Shortage in S. cerevisiae

Cited by 97 publications

References 39 publications

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

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

Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

Transcription termination by nuclear RNA polymerases

Contact Info

Product

Resources

About