Polysome arrest restricts miRNA turnover by preventing exosomal export of miRNA in growth-retarded mammalian cells

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Dynamic Proteomic and miRNA Analysis of Polysomes from Isolated Mouse Heart After Langendorff Perfusion
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Dynamic Proteomic and miRNA Analysis of Polysomes from Isolated Mouse Heart After Langendorff Perfusion

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Souvik Ghosh1, Mainak Bose1, Anirban Ray1

  • 1RNA Biology Research Laboratory, Molecular and Human Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India.

Molecular Biology of the Cell
|January 23, 2015
PubMed

Insights

Cellular microRNA (miRNA) stability increases with reduced proliferation, as growth-restricted cells sequester miRNA-protein complexes (miRNPs) on polysomes, decreasing target mRNA degradation and miRNA export.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • RNA Biology

Background:

  • MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression.
  • Tight control over miRNA abundance and turnover is crucial for cellular responses.
  • Regulated miRNA turnover optimizes cellular adaptation to external stimuli.

Purpose of the Study:

  • To investigate the relationship between cell proliferation and miRNA stability.
  • To understand the impact of cell growth on miRNA localization and function.
  • To elucidate mechanisms controlling miRNA turnover and activity.

Main Methods:

  • Analysis of mature miRNA stability in relation to cell proliferation rates.
  • Assessment of microribonucleoprotein (miRNP) association with polysomes in growth-restricted cells.
  • Evaluation of target messenger RNA (mRNA) degradation and exosomal miRNA export.

Main Results:

  • Mature miRNA stability inversely correlates with cell proliferation.
  • Growth-restricted mammalian cells exhibit increased miRNP association with polysomes.
  • Heightened polysome association reduces target mRNA degradation and impairs exosomal miRNA export.
  • Polysome sequestration increases cellular miRNA levels without enhancing miRNA activity.

Conclusions:

  • Subcellular distribution of miRNPs is a regulatory mechanism for miRNA activity and turnover.
  • Differential regulation of miRNPs based on cell growth impacts cellular miRNA homeostasis.
  • These findings provide insights into how cell proliferation influences miRNA-mediated gene regulation.

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