Noise in transcription negative feedback loops: simulation and experimental analysis

Abstract Background The regulatory feedback loops that present in structural and functional organization of molecular-genetic systems and the phenomenon of the regulatory signal delay, a time period between the moment of signal reception and its implementation, provide natural conditions for complicated dynamic regimes in these systems. The delay phenomenon at the intracellular level is a consequence of the matrix principle of data transmission, implemented through the rather complex processes of transcription and translation.However, the rules of the influence of system structure on system dynamics are not clearly understood. Knowledge of these rules is particularly important for construction of synthetic gene networks with predetermined properties. Results We study dynamical properties of models of simplest circular gene networks regulated by negative feedback mechanisms. We have shown existence and stability of oscillating trajectories (cycles) in these models. Two algorithms of construction and localization of these cycles have been proposed. For one of these models, we have solved an inverse problem of parameters identification. Conclusions The modeling results demonstrate that non-stationary dynamics in the models of circular gene networks with negative feedback loops is achieved by a high degree of non-linearity of the mechanism of the autorepressor influence on its own expression, by the presence of regulatory signal delay, the value of which must exceed a certain critical value, and transcription/translation should be initiated from a sufficiently strong promoter/Shine-Dalgarno site. We believe that the identified patterns are key elements of the oscillating construction design.

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Stability and Hopf bifurcation analysis in a delayed three-node circuit involving interlinked positive and negative feedback loops

Mathematical Biosciences ◽

10.1016/j.mbs.2018.11.003 ◽

2019 ◽

Vol 310 ◽

pp. 50-64 ◽

Cited By ~ 2

Author(s):

Guiyuan Wang ◽

Zhuoqin Yang ◽

Marc Turcotte

Keyword(s):

Hopf Bifurcation ◽

Negative Feedback ◽

Bifurcation Analysis ◽

Feedback Loops ◽

Negative Feedback Loops ◽

Positive And Negative Feedback

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Emerging trends: Reviewing the reviewers (again)

Natural Language Engineering ◽

10.1017/s1351324920000030 ◽

2020 ◽

Vol 26 (2) ◽

pp. 245-257

Author(s):

Kenneth Ward Church

Keyword(s):

Social Media ◽

Negative Feedback ◽

Feedback Loops ◽

Business Meeting ◽

Negative Feedback Loops ◽

Emerging Trends ◽

Over Time

AbstractThe ACL-2019 Business meeting ended with a discussion of reviewing. Conferences are experiencing a success catastrophe. They are becoming bigger and bigger, which is not only a sign of success but also a challenge (for reviewing and more). Various proposals for reducing submissions were discussed at the Business meeting. IMHO, the problem is not so much too many submissions, but rather, random reviewing. We cannot afford to do reviewing as badly as we do (because that leads to even more submissions). Negative feedback loops are effective. The reviewing process will improve over time if reviewers teach authors how to write better submissions, and authors teach reviewers how to write more constructive reviews. If you have received a not-ok (unhelpful/offensive) review, please help program committees improve by sharing your not-ok reviews on social media.

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MAPK modulation of yeast pheromone signaling output and the role of phosphorylation sites in the scaffold protein Ste5

Molecular Biology of the Cell ◽

10.1091/mbc.e18-12-0793 ◽

2019 ◽

Vol 30 (8) ◽

pp. 1037-1049 ◽

Cited By ~ 2

Author(s):

Matthew J. Winters ◽

Peter M. Pryciak

Keyword(s):

Negative Feedback ◽

Scaffold Protein ◽

Feedback Loops ◽

Phosphorylation Sites ◽

Pheromone Response ◽

Pheromone Response Pathway ◽

Negative Feedback Loops ◽

Pheromone Signaling ◽

Mitogen Activated Protein

Mitogen-activated protein kinases (MAPKs) mediate numerous eukaryotic signaling responses. They also can modulate their own signaling output via positive or negative feedback loops. In the yeast pheromone response pathway, the MAPK Fus3 triggers negative feedback that dampens its own activity. One target of this feedback is Ste5, a scaffold protein that promotes Fus3 activation. Binding of Fus3 to a docking motif (D motif) in Ste5 causes signal dampening, which was proposed to involve a central cluster of phosphorylation sites in Ste5. Here, we reanalyzed the role of these central sites. Contrary to prior claims, phosphorylation-mimicking mutations at these sites did not impair signaling. Also, the hyperactive signaling previously observed when these sites were mutated to nonphosphorylatable residues arose from their replacement with valine residues and was not observed with other substitutes. Instead, a cluster of N-terminal sites in Ste5, not the central sites, is required for the rapid dampening of initial responses. Further results suggest that the role of the Fus3 D motif is most simply explained by a tethering effect that promotes Ste5 phosphorylation, rather than an allosteric effect proposed to regulate Fus3 activity. These findings substantially revise our understanding of how MAPK feedback attenuates scaffold-mediated signaling in this model pathway.

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