Phenotypic noise: effects of post‐transcriptional regulatory processes affecting <scp>mRNA</scp>

Arbel-Goren, Rinat; Tal, Asaf; Stavans, Joel

doi:10.1002/wrna.1209

Cited by 9 publications

(7 citation statements)

References 92 publications

(162 reference statements)

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“…Of note, interindividual variability was much higher at the mRNA level than at the protein level (Supplemental Table 3), which is likely a consequence of mRNA regulation or clearance and the high stability of protein (commonly observed for other genes; ref. 20).…”

Section: Resultsmentioning

confidence: 99%

Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases

Dragin¹,

Bismuth²,

Cizeron-Clairac³

et al. 2016

Journal of Clinical Investigation

162

117

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Autoimmune diseases affect 5% to 8% of the population, and females are more susceptible to these diseases than males. Here, we analyzed human thymic transcriptome and revealed sex-associated differences in the expression of tissue-specific antigens that are controlled by the autoimmune regulator (AIRE), a key factor in central tolerance. We hypothesized that the level of AIRE is linked to sexual dimorphism susceptibility to autoimmune diseases. In human and mouse thymus, females expressed less AIRE (mRNA and protein) than males after puberty. These results were confirmed in purified murine thymic epithelial cells (TECs). We also demonstrated that AIRE expression is related to sexual hormones, as male castration decreased AIRE thymic expression and estrogen receptor α-deficient mice did not show a sex disparity for AIRE expression. Moreover, estrogen treatment resulted in downregulation of AIRE expression in cultured human TECs, human thymic tissue grafted to immunodeficient mice, and murine fetal thymus organ cultures. AIRE levels in human thymus grafted in immunodeficient mice depended upon the sex of the recipient. Estrogen also upregulated the number of methylated CpG sites in the AIRE promoter. Together, our results indicate that in females, estrogen induces epigenetic changes in the AIRE gene, leading to reduced AIRE expression under a threshold that increases female susceptibility to autoimmune diseases.

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Section: Resultsmentioning

confidence: 99%

Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases

Dragin¹,

Bismuth²,

Cizeron-Clairac³

et al. 2016

Journal of Clinical Investigation

162

117

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“…RNA-binding protein(s) and small RNAs, have an intrinsic modulatory potential. It is known that post-transcriptional regulation allows both an ON/OFF switch and fine-tuned control of gene expression [29]. RsmA (and its homologue RsmN) shows a wide range of binding affinities for its mRNA targets and high affinity for its titrating small RNAs (RsmY/Z) [30,31].…”

Section: The Gac/rsm Cascade As Lifestyle Modulatormentioning

confidence: 99%

Lifestyle transitions and adaptive pathogenesis of Pseudomonas aeruginosa

Valentini

González

Mavridou

et al. 2018

Current Opinion in Microbiology

147

140

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Pseudomonas aeruginosa acute and chronic infections are of great concern to human health, especially in hospital settings. It is currently assumed that P. aeruginosa has two antagonistic pathogenic strategies that parallel two different lifestyles; free-living cells are predominantly cytotoxic and induce an acute inflammatory reaction, while biofilm-forming communities cause refractory chronic infections. Recent findings suggest that the planktonic-to-sessile transition is a complex, reversible and overall dynamic differentiation process. Here, we examine how the Gac/Rsm regulatory cascade, a key player in this lifestyle switch, endows P. aeruginosa with both a permissive lifecycle in nature and flexible virulence strategy during infection.

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“…when the production rates of the sRNA and an mRNA target are comparable (7,9,10). Intrinsic noise is the cell-to-cell variation in gene expression of genetically identical cells (11–16), stemming from the stochastic nature of biochemical processes such as transcription and translation (17). Enhanced stoichiometric fluctuations are different from those due to small numbers, which are expected to dominate noise as sRNA production increases deeper into the silenced regime.…”

Section: Introductionmentioning

confidence: 99%

Transcript degradation and noise of small RNA-controlled genes in a switch activated network inEscherichia coli

et al. 2016

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Post-transcriptional regulatory processes may change transcript levels and affect cell-to-cell variability or noise. We study small-RNA downregulation to elucidate its effects on noise in the iron homeostasis network of Escherichia coli. In this network, the small-RNA RyhB undergoes stoichiometric degradation with the transcripts of target genes in response to iron stress. Using single-molecule fluorescence in situ hybridization, we measured transcript numbers of the RyhB-regulated genes sodB and fumA in individual cells as a function of iron deprivation. We observed a monotonic increase of noise with iron stress but no evidence of theoretically predicted, enhanced stoichiometric fluctuations in transcript numbers, nor of bistable behavior in transcript distributions. Direct detection of RyhB in individual cells shows that its noise is much smaller than that of these two targets, when RyhB production is significant. A generalized two-state model of bursty transcription that neglects RyhB fluctuations describes quantitatively the dependence of noise and transcript distributions on iron deprivation, enabling extraction of in vivo RyhB-mediated transcript degradation rates. The transcripts’ threshold-linear behavior indicates that the effective in vivo interaction strength between RyhB and its two target transcripts is comparable. Strikingly, the bacterial cell response exhibits Fur-dependent, switch-like activation instead of a graded response to iron deprivation.

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Phenotypic noise: effects of post‐transcriptional regulatory processes affecting mRNA

Cited by 9 publications

References 92 publications

Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases

Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases

Lifestyle transitions and adaptive pathogenesis of Pseudomonas aeruginosa

Transcript degradation and noise of small RNA-controlled genes in a switch activated network inEscherichia coli

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