Of Gene Expression and Cell Division Time: A Mathematical Framework for Advanced Differential Gene Expression and Data Analysis

Baum, Katharina; Schuchhardt, Johannes; Wolf, Jana; Busse, Dorothea

doi:10.1016/j.cels.2019.07.009

Cited by 11 publications

(10 citation statements)

References 39 publications

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“… (A) A basic gene expression model with key parameters (adapted from REF. [ 56 , 92 ]). The mRNA is transcribed with rate V sr and degraded with a half-life represented by t r1/2 .…”

Section: Resultsmentioning

confidence: 99%

“…(C) Mathematical expression of mRNA (Eq 1) and protein abundances (Eq 2) as a function of key gene expression parameters, including cell doubling time T cc , as detailed in REF. [ 92 ]. Rearranging Eq 2 yields the dependency of protein-mRNA abundance ratio on the translation rate constant K sp , cell doubling time T cc , and protein half-life t p1/2 (Eq 3).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

Min

Jannace

et al. 2021

PLoS Pathog

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Microbial pathogens grow in a wide range of different morphologies that provide distinct advantages for virulence. In the fungal pathogen Candida albicans, adenylyl cyclase (Cyr1) is thought to be a master regulator of the switch to invasive hyphal morphogenesis and biofilm formation. However, faster growing cyr1Δ/Δ pseudorevertant (PR) mutants were identified that form hyphae in the absence of cAMP. Isolation of additional PR mutants revealed that their improved growth was due to loss of one copy of BCY1, the negative regulatory subunit of protein kinase A (PKA) from the left arm of chromosome 2. Furthermore, hyphal morphogenesis was improved in some of PR mutants by multigenic haploinsufficiency resulting from loss of large regions of the left arm of chromosome 2, including global transcriptional regulators. Interestingly, hyphal-associated genes were also induced in a manner that was independent of cAMP. This indicates that basal protein kinase A activity is an important prerequisite to induce hyphae, but activation of adenylyl cyclase is not needed. Instead, phosphoproteomic analysis indicated that the Cdc28 cyclin-dependent kinase and the casein kinase 1 family member Yck2 play key roles in promoting polarized growth. In addition, integrating transcriptomic and proteomic data reveals hyphal stimuli induce increased production of key transcription factors that contribute to polarized morphogenesis.

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“… (A) A basic gene expression model with key parameters (adapted from REF. [ 56 , 92 ]). The mRNA is transcribed with rate V sr and degraded with a half-life represented by t r1/2 .…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

Min

Jannace

et al. 2021

PLoS Pathog

View full text Add to dashboard Cite

show abstract

“…Taking the division rate into account is extremely important, not just for comparing systems for which cell division rates vary greatly, but for accurately detecting the kdeg of proteins that turn over slowly, which can be confounded by kdil (24). More detail about the non-trivial relationship between protein synthesis, degradation rate, and cell division rate are discussed in depth in a recent publication by the Busse group, who emphasize that taking the cell division rate into account significantly improves the "hit rate" of differential gene expression profiling (30).…”

Section: Cell Division and Protein Turnovermentioning

confidence: 99%

Proteome Turnover in the Spotlight: Approaches, Applications, and Perspectives

Ross¹,

Langer²,

Jovanović³

2021

Molecular & Cellular Proteomics

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In all cells, proteins are continuously synthesized and degraded in order to maintain protein homeostasis and modify gene expression levels in response to stimuli. Collectively, the processes of protein synthesis and degradation are referred to as protein turnover. At steady state, protein turnover is constant to maintain protein homeostasis, but in dynamic responses, proteins change their rates of synthesis and degradation in order to adjust their proteomes to internal or external stimuli. Thus, probing the kinetics and dynamics of protein turnover lends insight into how cells regulate essential processes such as growth, differentiation, and stress response. Here we outline historical and current approaches to measuring the kinetics of protein turnover on a proteome-wide scale in both steady-state and dynamic systems, with an emphasis on metabolic tracing using stable-isotope-labeled amino acids. We highlight important considerations for designing proteome turnover experiments, key biological findings regarding the conserved principles of proteome turnover regulation, and future perspectives for both technological and biological investigation.

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“… a , A basic gene expression model with key parameters (adopted from REF. 52, 83 ). The mRNA is transcribed with rate V sr and degraded with a half-life represented by t r1/2 .…”

Section: Resultsmentioning

confidence: 99%

“… c , Mathematical expression of mRNA (Equation 1) and protein abundances (Equation 2) as a function of key gene expression parameters, including cell doubling time T cc , as detailed in REF. 83 . Rearranging Equation 2 yields the dependency of protein-mRNA abundance ratio on the translation rate constant K sp , cell doubling time T cc , and protein half-life t p1/2 (Equation 3).…”

Section: Resultsmentioning

confidence: 99%

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

Min

Jannace

et al. 2021

Preprint

View full text Add to dashboard Cite

Microbial pathogens grow in a wide range of different morphologies that provide distinct advantages for virulence. In the fungal pathogen Candida albicans, adenylyl cyclase (Cyr1) has been thought to be a master regulator of the switch to invasive hyphal morphogenesis and biofilm formation. However, faster growing cyr1Δ/Δ pseudorevertant (PR) mutants were identified that form hyphae in the absence of cAMP. Isolation of additional PR mutants revealed that their improved growth was due to loss of one copy of BCY1, the negative regulatory subunit of protein kinase A, from the left arm of chromosome 2. Furthermore, hyphal morphogenesis was improved in some of PR mutants by multigenic haploinsufficiency resulting from loss of large regions of the left arm of chromosome 2, including global transcriptional regulators. Interestingly, hyphal-associated genes were also induced in a manner that was independent of cAMP. This indicates that basal protein kinase A activity is an important prerequisite to induce hyphae, but activation of the cAMP pathway is not needed. Instead, phosphoproteomic analysis indicated that the Cdc28 cyclin-dependent kinase and the casein kinase Yck2 play key roles in promoting polarized growth. In addition, integrating transcriptomic and proteomic data reveals hyphal stimuli induce increased production of key transcription factors that contribute to polarized morphogenesis.

show abstract

Of Gene Expression and Cell Division Time: A Mathematical Framework for Advanced Differential Gene Expression and Data Analysis

Cited by 11 publications

References 39 publications

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

Proteome Turnover in the Spotlight: Approaches, Applications, and Perspectives

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

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