Iron uptake and regulation in Schizosaccharomyces pombe

Labbé, Simon; Khan, Gulam Musawwir; Jacques, Jean-François

doi:10.1016/j.mib.2013.07.007

Cited by 51 publications

(71 citation statements)

References 58 publications

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“…Fission yeast has a finely tuned system of iron homeostasis entailing regulated expression of genes encoding proteins involved in iron uptake (10). Key players are the cell surface ferric reductase Frp1 that converts extracellular ferric ion to ferrous ion, which is then transported across the cell membrane by the oxidase-permease complex composed of Fio1 and Fip1 proteins.…”

Section: Resultsmentioning

confidence: 99%

“…The GATA-family transcription factor Fep1 represses expression of the aforementioned iron uptake genes under iron-replete growth conditions (10,14). Fep1 binds in an iron-dependent manner to a GATA sequence element [5′-ATC(A/T)GATA(A/T)] in the regulatory regions upstream of the repressible iron uptake genes.…”

Section: Resultsmentioning

confidence: 99%

“…These include, in addition to Fep1, the corepressors Tup11 and Tup12 (10,14). However, this scenario was vitiated by the findings that the Fep1, Tup11, and Tup12 mRNA levels, gauged by RNA-seq, were not affected significantly by the Y1F, S2A, Y1F•S7A, or S2A•S7A mutations (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…First, our studies highlight the role of Tyr1 and Ser2 in repressing the expression of multiple unlinked genes involved in iron uptake that comprise a Fep1-repressed regulon. Although the molecular details remain to be elucidated, we speculate that Fep1 bound to DNA flanking the target gene promoters might interact, through its C-terminal repressor domain (10) or corepressors bound to the repressor domain, with the Pol II CTD to exert a gene-specific repressive effect on transcription (or cotranscriptional RNA processing) and that this interaction depends on Tyr1 and Ser2.…”

Section: Discussionmentioning

confidence: 99%

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Individual letters of the RNA polymerase II CTD code govern distinct gene expression programs in fission yeast

Schwer

Bitton

Sánchez

et al. 2014

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

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The primary structure and phosphorylation pattern of the tandem Y 1 S 2 P 3 T 4 S 5 P 6 S 7 repeats of the RNA polymerase II carboxyl-terminal domain (CTD) comprise an informational code that coordinates transcription, chromatin modification, and RNA processing. To gauge the contributions of individual CTD coding "letters" to gene expression, we analyzed the poly(A) + transcriptomes of fission yeast mutants that lack each of the four inessential CTD phosphoacceptors: Tyr1, Ser2, Thr4, and Ser7. There was a hierarchy of CTD mutational effects with respect to the number of dysregulated protein-coding RNAs, with S2A (n = 227) >> Y1F (n = 71) > S7A (n = 58) >> T4A (n = 7). The majority of the protein-coding RNAs affected in Y1F cells were coordinately affected by S2A, suggesting that Tyr1-Ser2 constitutes a two-letter code "word." Y1F and S2A elicited increased expression of genes encoding proteins involved in iron uptake (Frp1, Fip1, Fio1, Str3, Str1, Sib1), without affecting the expression of the genes that repress the iron regulon, implying that Tyr1-Ser2 transduces a repressive signal. Y1F and S2A cells had increased levels of ferric reductase activity and were hypersensitive to phleomycin, indicative of elevated intracellular iron. The T4A and S7A mutations had opposing effects on the phosphate response pathway. T4A reduced the expression of two genes encoding proteins involved in phosphate acquisition (the Pho1 acid phosphatase and the phosphate transporter SPBC8E4.01c), without affecting the expression of known genes that regulate the phosphate response pathway, whereas S7A increased pho1 + expression. These results highlight specific cellular gene expression programs that are responsive to distinct CTD cues.iron homeostasis | phosphate homeostasis | transcription profiling T he carboxyl-terminal domain (CTD) of the Rpb1 subunit of RNA polymerase II (Pol II) consists of tandemly repeated heptapeptides of consensus sequence Y 1 S 2 P 3 T 4 S 5 P 6 S 7 . The inherently plastic CTD structure is modulated by phosphorylation of the Tyr1, Ser2, Thr4, Ser5, and Ser7 residues and by cis-trans isomerization of the prolines (1, 2). With as many as 128 n potential CTD primary structures (where n is the number of heptads), the CTD provides information about the state of the transcription machinery-a CTD code-that is "read" by CTD receptor proteins that control transcription, modify chromatin structure, and catalyze or regulate mRNA capping, splicing, and polyadenylation (1, 2).Basic informational rules that govern the CTD code have been elucidated by genetically manipulating the composition and structure of the Rpb1 CTD in the fission yeast Schizosaccharomyces pombe (3-7). By introducing alanines and conservative mutations in lieu of Tyr1, Ser2, Pro3, Thr4, Ser5, Pro6, and Ser7 of every consensus heptad of a fully functional Rpb1 CTD array (comprising 14 consensus heptad repeats linked to the body of Rpb1 by a "rump" consisting of four degenerate heptads), we determined that: (i) Tyr1, Pro3, Ser5, and Pro6 are essential ...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Individual letters of the RNA polymerase II CTD code govern distinct gene expression programs in fission yeast

Schwer

Bitton

Sánchez

et al. 2014

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

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show abstract

“…This was the case for the Y1F and S2A mutations. The most striking expression signature of the Y1F and S2A alleles was the derepression of the multigene iron homeostasis regulon , which is normally silenced under iron-replete conditions by the DNA-binding transcription factor Fep1 (Labbé et al 2013). We proposed that the two-letter CTD Tyr1-Ser2 coding word is necessary to transduce a repressive signal from Fep1 to the transcription apparatus.…”

Section: Discussionmentioning

confidence: 99%

RNA polymerase II CTD phospho-sites Ser5 and Ser7 govern phosphate homeostasis in fission yeast

Schwer

Sánchez

Shuman

2015

RNA

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Phosphorylation of the tandem YSPTSPS repeats of the RNA polymerase II CTD inscribes an informational code that orchestrates eukaryal mRNA synthesis. Here we interrogate the role of the CTD in phosphate homeostasis in fission yeast. Expression of Pho1 acid phosphatase, which is repressed during growth in phosphate-rich medium and induced by phosphate starvation, is governed strongly by CTD phosphorylation status, but not by CTD repeat length. Inability to place a Ser7-PO 4 mark (as in S7A) results in constitutive derepression of Pho1 expression in phosphate-replete medium. In contrast, indelible installation of a Ser7-PO 4 mimetic (as in S7E) hyper-represses Pho1 in phosphate-replete cells and inhibits Pho1 induction during starvation. Pho1 phosphatase is derepressed by ablation of the CTD Ser5-PO 4 mark, achieved either by mutating Ser5 in all consensus heptads to alanine, or replacing all Pro6 residues with alanine. We find that Ser5 status is a tunable determinant of Pho1 regulation, i.e., serial decrements in the number of consensus Ser5 heptads from seven to two elicits a progressive increase in Pho1 expression in phosphate-replete medium. Pho1 is also derepressed by hypomorphic mutations of the CTD kinase Cdk9. Inactivation of the CTD phosphatase Ssu72 attenuates Pho1 induction in wild-type cells and blocks Pho1 derepression in S7A cells. These experiments implicate Ser5, Pro6, and Ser7 as component letters of a CTD coding "word" that transduces a repressive transcriptional signal via serine phosphorylation.

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Iron Uptake by Plants and Fungi

2016

Iron Metabolism

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Iron uptake and regulation in Schizosaccharomyces pombe

Cited by 51 publications

References 58 publications

Individual letters of the RNA polymerase II CTD code govern distinct gene expression programs in fission yeast

Individual letters of the RNA polymerase II CTD code govern distinct gene expression programs in fission yeast

RNA polymerase II CTD phospho-sites Ser5 and Ser7 govern phosphate homeostasis in fission yeast

Iron Uptake by Plants and Fungi

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