Quantitative Analysis of Fission Yeast Transcriptomes and Proteomes in Proliferating and Quiescent Cells

Marguerat, Samuel; Schmidt, Manuela; Codlin, Sandra; Chen, Wei; Aebersold, Ruedi; Bähler, Jürg

doi:10.1016/j.cell.2012.09.019

Cited by 522 publications

(589 citation statements)

References 68 publications

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“…RNA-seq affords a detailed strand-specific annotated map of the protein-coding and noncoding fission yeast transcripts vs. their genomic DNA loci (11)(12)(13). Here we performed RNA-seq on poly(A) + RNA isolated from cells expressing Rpb1 with CTDs composed of the rump plus 14 consensus YSPTSPS heptads or an identical number of Y1F, S2A, T4A, or S7A mutant heptads (6).…”

Section: Resultsmentioning

confidence: 99%

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%

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.

Self Cite

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show abstract

“…We found values for mean mRNA levels (m), mean protein levels (p), mRNA decay rates (d 2 ) and protein decay rates (d 4 ) for 2390 different unique genes from experimental papers (Marguerat et al, 2012;Amorim et al, 2010;Christiano et al, 2014). These parameters and the correlations between them are displayed in Figure 7.…”

Section: Schizosaccharomyces Pombe Parameter Studymentioning

confidence: 99%

“…It is clear from this figure that there exists a strong correlation between mean mRNA and protein levels and weak correlation between the other parameters. (Marguerat et al, 2012;Amorim et al, 2010;Christiano et al, 2014). Histograms are shown on diagonal panels and scatter plots comparing parameters are shown on off-diagonal panels.…”

Section: Schizosaccharomyces Pombe Parameter Studymentioning

confidence: 99%

“…However, it is possible to see a few genes for which the protein decay rate is relatively slow and the correlation distance exceeds 0.2. Figure 8: Distance correlation (computed using equation (14)) comparing noise comparison results for slow protein degradation case and fast protein degradation with 2390 unique S. Pombe parameter sets (Marguerat et al, 2012;Amorim et al, 2010;Christiano et al, 2014). Black lines highlight distances of 0.2 for slow and fast protein degradation cases.…”

Section: Schizosaccharomyces Pombe Parameter Studymentioning

confidence: 99%

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The influence of nuclear compartmentalisation on stochastic dynamics of self-repressing gene expression

Sturrock

Shahrezaei

2017

Journal of Theoretical Biology

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Gene expression is an inherently noisy process. This noise is generally thought to be deleterious as precise internal regulation of biochemical reactions is essential for cell growth and survival. Selfrepression of gene expression, which is the simplest form of a negative feedback loop, is commonly believed to be employed by cellular systems to decrease the stochastic fluctuations in gene expression. When there is some delay in autoregulation, it is also believed that this system can generate oscillations. In eukaryotic cells, mRNAs that are synthesised in the nucleus must be exported to the cytoplasm to function in protein synthesis, whereas proteins must be transported into the nucleus from the cytoplasm to regulate the expression levels of genes. Nuclear transport thus plays a critical role in eukaryotic gene expression and regulation. Some recent studies have suggested that nuclear retention of mRNAs can control noise in mRNA expression. However, the effect of nuclear transport on protein noise and its interplay with negative feedback regulation is not completely understood. In this paper, we systematically compare four different simple models of gene expression. By using simulations and applying the linear noise approximation to the corresponding chemical master equations, we investigate the influence of nuclear import and export on noise in gene expression in a negative autoregulatory feedback loop. We first present results consistent with the literature, i.e., that negative feedback can effectively buffer the variability in protein levels, and nuclear retention can decrease mRNA noise levels. Interestingly we find that when negative feedback is combined with nuclear retention, an amplification in gene expression noise can be observed and is dependant on nuclear translocation rates. Finally, we investigate the effect of nuclear compartmentalisation on the ability of self-repressing genes to exhibit stochastic oscillatory dynamics.

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“…(SMN-Gem2) 2 ] is the basal functional unit. Using in vivo estimates of SMN protein concentration, 116 Van Duyne and colleagues calculated that the concentration of the dimer (»15 nM) lies far, far below the dissociation constant of SMN tetramers (»1 uM). 102 Immunofluorescence studies showed that yeast SMN is diffusely distributed throughout the nucleus and cytoplasm, with no discernible foci.…”

Section: Oligomeric Properties Of Smn Complexesmentioning

confidence: 99%

SMN - A chaperone for nuclear RNP social occasions?

2016

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Survival Motor Neuron (SMN) protein localizes to both the nucleus and the cytoplasm. Cytoplasmic SMN is diffusely localized in large oligomeric complexes with core member proteins, called Gemins. Biochemical and cell biological studies have demonstrated that the SMN complex is required for the cytoplasmic assembly and nuclear transport of Sm-class ribonucleoproteins (RNPs). Nuclear SMN accumulates with spliceosomal small nuclear (sn)RNPs in Cajal bodies, sub-domains involved in multiple facets of snRNP maturation. Thus, the SMN complex forms stable associations with both nuclear and cytoplasmic snRNPs, and plays a critical role in their biogenesis. In this review, we focus on potential functions of the nuclear SMN complex, with particular emphasis on its role within the Cajal body.

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Quantitative Analysis of Fission Yeast Transcriptomes and Proteomes in Proliferating and Quiescent Cells

Cited by 522 publications

References 68 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

The influence of nuclear compartmentalisation on stochastic dynamics of self-repressing gene expression

SMN - A chaperone for nuclear RNP social occasions?

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