Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in <i>Saccharomyces cerevisiae</i>

Ljungdahl, Per O.; Daignan‐Fornier, Bertrand

doi:10.1534/genetics.111.133306

Cited by 462 publications

(542 citation statements)

References 422 publications

(438 reference statements)

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“…This study focuses on the well-studied reporter gene URA3 that encodes orotidine-5′-phosphate decarboxylase of the pyrimidine biosynthetic pathway. The gene is expressed at low basal levels in rich media and induced severalfold by a transcriptional activator upon uracil depletion (26). The domain of chromosome V that bears URA3 has frequently been used as a reporter of genome-wide cohesion (1).…”

Section: Resultsmentioning

confidence: 99%

Binding, sliding, and function of cohesin during transcriptional activation

Borrie

Campor

Joshi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The ring-shaped cohesin complex orchestrates long-range DNA interactions to mediate sister chromatid cohesion and other aspects of chromosome structure and function. In the yeast Saccharomyces cerevisiae, the complex binds discrete sites along chromosomes, including positions within and around genes. Transcriptional activity redistributes the complex to the 3′ ends of convergently oriented gene pairs. Despite the wealth of information about where cohesin binds, little is known about cohesion at individual chromosomal binding sites and how transcription affects cohesion when cohesin complexes redistribute. In this study, we generated extrachromosomal DNA circles to study cohesion in response to transcriptional induction of a model gene, URA3. Functional cohesin complexes loaded onto the locus via a poly(dA:dT) tract in the gene promoter and mediated cohesion before induction. Upon transcription, the fate of these complexes depended on whether the DNA was circular or not. When gene activation occurred before DNA circularization, cohesion was lost. When activation occurred after DNA circularization, cohesion persisted. The presence of a convergently oriented gene also prevented transcription-driven loss of functional cohesin complexes, at least in M phase-arrested cells. The results are consistent with cohesin binding chromatin in a topological embrace and with transcription mobilizing functional complexes by sliding them along DNA.T he protein complex known as cohesin organizes eukaryotic genomes into structures that segregate faithfully between dividing cells. The complex was first discovered for its role in mediating sister chromatid cohesion, but it is now known to participate in numerous aspects of chromosome biology (1, 2). Cohesin is clinically relevant because mutations in subunits of the complex or in factors that load and activate the complex lead to developmental disorders such as Cornelia de Lange syndrome, Roberts syndrome, and Warsaw breakage syndrome (3, 4).Cohesin is a ring-shaped complex composed of four subunits named Smc1, Smc3, Scc3, and Mcd1/Scc1 in budding yeast. The complex is thought to embrace DNA topologically with chromatin fibers passing through a central open channel (5-7). A substantial body of work supports a model in which cohesion arises from single cohesin complexes that embrace both sister chromatids [the double embrace model (6)]. Whether the central channel is large enough to accommodate both chromatids has recently been brought into question (8). In addition, the behavior of cohesin has not always been consistent with a double embrace by single complexes (for examples, see refs. 9-11). These situations usually involve a perturbation that causes loss of cohesion but not a loss of cohesin binding from chromatin. Such results force consideration of alternative models in which cohesin complexes embrace only one chromatid topologically and interact with other cohesin complexes or chromatin features to mediate cohesion (9,11,12).Cohesin binds densely in centromeric regions of chromos...

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Section: Resultsmentioning

confidence: 99%

Binding, sliding, and function of cohesin during transcriptional activation

Borrie

Campor

Joshi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Saccharomyces cerevisiae prefers ammonia or glutamine as a source of nitrogen but can use a variety of alternative, nonpreferred nitrogen sources (46). Nitrogen availability regulates growth, metabolism, and transcription through a complex interplay of multiple pathways (46,56,57). The target of rapamycin complex 1 (TORC1) stimulates expression of growth-related genes in part through the sensing of intracellular amino acid levels (57,58).…”

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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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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“…For further sequence analysis, we considered only core members of the AAP family from S. cerevisiae (1). These are the same 18 proteins classified by Saier (2) as belonging to the yeast amino acid transporter family.…”

Section: Methodsmentioning

confidence: 99%

“…AAPs, a subset belonging to the MFS family (1). An alignment of the C termini of AAP sequences (see "Experimental Procedures") showed conserved clusters of aromatic residues at the beginning and at the end of the sequences together with alternating positively and negatively charged clusters ( Fig.…”

Section: Termini Of Amino Acid Transporters In the Plasma Membrane mentioning

confidence: 99%

A Plasma Membrane Association Module in Yeast Amino Acid Transporters

Popov‐Čeleketić¹,

Bianchi²,

Ruiz

et al. 2016

Journal of Biological Chemistry

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Amino acid permeases (AAPs) in the plasma membrane (PM) of Saccharomyces cerevisiae are responsible for the uptake of amino acids and involved in regulation of their cellular levels. Here, we report on a strong and complex module for PM association found in the C-terminal tail of AAPs. Using in silico analyses and mutational studies we found that the C-terminal sequences of Gap1, Bap2, Hip1, Tat1, Tat2, Mmp1, Sam3, Agp1, and Gnp1 are about 50 residues long, associate with the PM, and have features that discriminate them from the termini of organellar amino acid transporters. We show that this sequence (named PM asseq ) contains an amphipathic ␣-helix and the FWC signature, which is palmitoylated by palmitoyltransferase Pfa4. Variations of PM asseq , found in different AAPs, lead to different mobilities and localization patterns, whereas the disruption of the sequence has an adverse effect on cell viability. We propose that PM asseq modulates the function and localization of AAPs along the PM. PM asseq is one of the most complex protein signals for plasma membrane association across species and can be used as a delivery vehicle for the PM.Yeast transport amino acids across the plasma membrane (PM), 4 the vacuolar membrane (VM), and to a lesser extent the mitochondrial membrane (1). In the plasma and vacuolar membranes, there are 22 and 11 secondary amino acid transporters, respectively. These transporters are polytopic membrane proteins with 10 -14 transmembrane segments. They belong to three superfamilies: amino acid/polyamine/organocation (APC), major facilitator superfamily (MFS), and amino acid/ polyamine transporter II (AAPTII) (2). The amino acid transporters belonging to the APC superfamily are often referred to as amino acid permeases (AAPs). They are mainly localized in the PM and can be highly specific, e.g. transport only one (enantiomer) amino acid or have a broad range of substrates, like the general amino acid permease Gap1.Alongside the transporter function, additional roles have been proposed for some AAPs. The most prominent example is Gap1, which has a receptor function whereby it signals the protein kinase A (PKA) pathway (3). This so-called transceptor function has also been described for the phosphate transporter Pho84 and the ammonium transporter Mep2 but not for any other AAPs (4, 5). On the other end of the spectrum is Ssy1, an endoplasmic reticulum (ER)-resident AAP member, that plays a role in amino acid sensing but has no transport function (6 -8). The levels of AAPs at the PM are modulated by several transcriptional and post-translational control mechanisms, e.g. nitrogen catabolite repression, general amino acid control, and substrate/stress-induced endocytosis (9 -12). Although for several AAPs many details of these control mechanisms have been elucidated, quite a few questions concerning the spatiotemporal regulation of AAPs remain unanswered. Which mechanism ensures that the function is performed in the right organelle and what determines the positioning of transporters within diff...

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

Cited by 462 publications

References 422 publications

Binding, sliding, and function of cohesin during transcriptional activation

Binding, sliding, and function of cohesin during transcriptional activation

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

A Plasma Membrane Association Module in Yeast Amino Acid Transporters

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