Single‐cell mRNA profiling reveals the hierarchical response of miRNA targets to miRNA induction

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2018
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Rzepiela, Andrzej J.
Ghosh, Souvik
Breda, Jeremie
Vina-Vilaseca, Arnau
Syed, Afzal P.
Eschbach, Katja
Beisel, Christian
Nimwegen, Erik
Zavolan, Mihaela
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Molecular Systems Biology. Wiley. 2018, 14(8), e8266. eISSN 1744-4292. Available under: doi: 10.15252/msb.20188266
Zusammenfassung

miRNAs are small RNAs that regulate gene expression post‐transcriptionally. By repressing the translation and promoting the degradation of target mRNAs, miRNAs may reduce the cell‐to‐cell variability in protein expression, induce correlations between target expression levels, and provide a layer through which targets can influence each other's expression as “competing RNAs” (ceRNAs). However, experimental evidence for these behaviors is limited. Combining mathematical modeling with RNA sequencing of individual human embryonic kidney cells in which the expression of two distinct miRNAs was induced over a wide range, we have inferred parameters describing the response of hundreds of miRNA targets to miRNA induction. Individual targets have widely different response dynamics, and only a small proportion of predicted targets exhibit high sensitivity to miRNA induction. Our data reveal for the first time the response parameters of the entire network of endogenous miRNA targets to miRNA induction, demonstrating that miRNAs correlate target expression and at the same time increase the variability in expression of individual targets across cells. The approach is generalizable to other miRNAs and post‐transcriptional regulators to improve the understanding of gene expression dynamics in individual cell types.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
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ceRNA; Michaelis–Menten constant; miRNA regulation; scRNA-Seq;target down-regulation
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ISO 690RZEPIELA, Andrzej J., Souvik GHOSH, Jeremie BREDA, Arnau VINA-VILASECA, Afzal P. SYED, Andreas J. GRUBER, Katja ESCHBACH, Christian BEISEL, Erik NIMWEGEN, Mihaela ZAVOLAN, 2018. Single‐cell mRNA profiling reveals the hierarchical response of miRNA targets to miRNA induction. In: Molecular Systems Biology. Wiley. 2018, 14(8), e8266. eISSN 1744-4292. Available under: doi: 10.15252/msb.20188266
BibTex
@article{Rzepiela2018-08-27Singl-50939,
  year={2018},
  doi={10.15252/msb.20188266},
  title={Single‐cell mRNA profiling reveals the hierarchical response of miRNA targets to miRNA induction},
  number={8},
  volume={14},
  journal={Molecular Systems Biology},
  author={Rzepiela, Andrzej J. and Ghosh, Souvik and Breda, Jeremie and Vina-Vilaseca, Arnau and Syed, Afzal P. and Gruber, Andreas J. and Eschbach, Katja and Beisel, Christian and Nimwegen, Erik and Zavolan, Mihaela},
  note={Article Number: e8266}
}
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