microRNA-mediated noise processing in cells: A fight or a game?

Ferro, Elsi; Bena, Chiara Enrico; Grigolon, Silvia; Bosia, Carla

doi:10.1016/j.csbj.2020.02.020

Cited by 8 publications

(8 citation statements)

References 85 publications

(134 reference statements)

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“…Thus, despite proposed methods [19, 20], we lack this information for mouse microRNAs. Nevertheless, considering the lengths of pre-miRNAs, which are about 70 nucleotides [21], gives an approximate lower bound: L μ ,pri ≥ L μ ,pre = 70, which yields to σ ϵ = 0.0014 (note that this is a strict underestimation). Since the energetic costs of assembling miRNA are expected to be smaller than mRNA, we use σ ϵ = 0.5 as an upper bound.…”

Section: Supplemental Materialsmentioning

confidence: 99%

Bioenergetic costs and the evolution of noise regulation by microRNAs

İlker

Hinczewski

2023

Preprint

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Noise control, together with other regulatory functions facilitated by microRNAs (miRNAs), is believed to have played important roles in the evolution of multicellular eukaryotic organisms. miRNAs can dampen protein fluctuations via enhanced degradation of mRNAs, but this requires compensation by increased mRNA transcription to maintain the same expression levels. The overall mechanism is metabolically expensive, leading to questions about how it might have evolved in the first place. We develop a stochastic model of miRNA noise regulation, coupled with a detailed analysis of the associated metabolic costs. Additionally we calculate binding free energies for a range of miRNA seeds, the short sequences which govern target recognition. We argue that natural selection may have fine-tuned the Michaelis-Menten constant KM describing miRNA-mRNA affinity. KM is constrained by seed length, and we show that optimal noise control (minimum protein variance at a given energy cost) is achievable for seeds of 6-7 nucleotides in length, the most commonly observed types. Moreover, at optimality the degree of noise reduction approaches the theoretical bound set by the Wiener-Kolmogorov linear filter. The results illustrate how selective pressure toward energy efficiency has potentially shaped a crucial regulatory pathway in eukaryotes.

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Section: Supplemental Materialsmentioning

confidence: 99%

Bioenergetic costs and the evolution of noise regulation by microRNAs

İlker

Hinczewski

2023

Preprint

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“…206–231). In a similar way, while the noise in the gene expression is generally detrimental for the organism's fitness (Wang & Zhang, 2011), it can be locally controlled by micro‐ribonucleic acids (Ferro, Bena, Grigolon, & Bosia, 2020) and will only become life‐threatening if repeated systematically or compounded by poorly curable diseases such as HIV (Raser & O'Shea, 2005, p. 2011; Weinberger & Weinberger, 2013). In contrast, the noisy signaling in large homogeneous systems depending on centrally procured and and/or universally distributed information may cause a profound shock: in this respect, the crisis of the overstretched Ottoman Empire over the unintelligible guidance of the successive sultans in the 16th century is reminiscent of the stock market crashes in 1929 and 1987 due to the domination of noise trading over the informed trading (Kennedy, 1987, pp.…”

Section: Noisy Signaling Redundancy and Semantic Inflation: How Complex Systems Pick Themselves Apartmentioning

confidence: 99%

Redundancy, Noisy Signaling, and Semantic inflation: Studying the Patterns of Self‐Destruction in Complex Systems

Junge

Postoutenko

2020

Syst Res Behav Sci

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Across the natural and social world, some fairly advanced and apparently robust systems destroy themselves without discernible reason, function, or purpose. Whereas such and similar cases have been discussed within specific branches of scholarships, the attempts to propose and test a general theory of self-destruction in complex systems remain, to our knowledge, a thing of the future. To move in this direction, we suggest that the conflicts between explicit stratification, thorough functional differentiation and tacit segmentation within complex systems, are likely to provoke their unintended self-annihilation. Furthermore, we hypothesize that whenever such systems collapse, it is the circular co-dependency of noisy signaling, redundancy, and semantic inflation that sets self-destructive mechanisms in motion. We illustrate our preliminary findings with examples from social, natural, and artificial life; reexamine autoimmunity as a popular model of systemic self-destruction; and indicate potential avenues of empirical research aimed at supporting, qualifying or disproving the underlying hypothesis.

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“…MicroRNAs (miRNAs) are~22-nt noncoding RNAs that mediate the posttranscriptional regulation of their target genes by either translational repression or poly(A)-tail shortening (Ameres and Zamore, 2013;Bartel, 2018). Recently, researchers proposed that miRNAs can control gene expression noise and confer robustness to biological processes (Bartel and Chen, 2004;Schmiedel et al, 2015;Ebert and Sharp, 2012;Kasper et al, 2017;Ferro et al, 2020). miRNAs can reduce the noise of lowly expressed genes by accelerating mRNA turnover, which can be compensated for by higher transcription rates, and miRNAs can increase the noise of highly expressed genes by introducing additional extrinsic noise (Schmiedel et al, 2015).…”

Section: Introductionmentioning

confidence: 99%