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A Computational Pipeline for Intergenic/Intragenic Enhancer RNA Quantification in Mouse Embryonic Stem Cells
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A Computational Pipeline for Intergenic/Intragenic Enhancer RNA Quantification in Mouse Embryonic Stem Cells

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Extensive microRNA-mediated crosstalk between lncRNAs and mRNAs in mouse embryonic stem cells

Jennifer Y Tan1, Tamara Sirey2, Frantisek Honti1

  • 1MRC Functional Genomics Unit, University of Oxford, Oxford OX1 3QX, United Kingdom; University of Oxford, Department of Physiology, Anatomy and Genetics, Oxford OX1 3QX, United Kingdom; Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland;

Genome Research
|March 21, 2015
PubMed

Insights

Long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) interact via microRNAs (miRNAs). This study reveals prevalent, conserved miRNA-mediated crosstalk between lncRNAs and mRNAs in mouse embryonic stem cells, impacting development.

Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • Intergenic long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in gene regulation, including interactions with microRNAs (miRNAs).
  • The extent and functional impact of miRNA-mediated regulation of messenger RNA (mRNA) levels by lncRNAs remain largely unexplored.
  • Understanding lncRNA-mRNA-miRNA crosstalk is crucial for deciphering complex gene regulatory networks in development and disease.

Purpose of the Study:

  • To investigate the prevalence and functional consequences of miRNA-mediated crosstalk between lncRNAs and mRNAs.
  • To analyze transcriptome-wide changes induced by lncRNA knockdown in mouse embryonic stem cells (mESCs).
  • To experimentally validate the role of miRNAs in mediating lncRNA-mRNA interactions.

Main Methods:

  • Reanalysis of transcriptome-wide data from targeted knockdown of over 100 lncRNA transcripts in mESCs.
  • Experimental validation using temporal profiling of gene expression changes after loss of miRNA biogenesis in mESCs.
  • Bioinformatic analysis to identify shared miRNA response elements and functional enrichment of mRNA targets.

Main Results:

  • Approximately one-fifth of transcript level changes induced by lncRNAs were predicted to be miRNA-dependent.
  • >50% of lncRNAs and their miRNA-dependent mRNA targets coordinately upregulated upon miRNA depletion, supporting miRNA-mediated interaction.
  • lncRNAs involved in this crosstalk are predominantly cytoplasmic, share conserved miRNA response elements with targets, and target mRNAs with related biological functions.

Conclusions:

  • Post-transcriptional miRNA-mediated crosstalk between lncRNAs and mRNAs is prevalent and conserved in mammals.
  • This crosstalk significantly influences gene expression in mESCs and likely plays a role in critical developmental processes.
  • The findings highlight a novel layer of gene regulation involving lncRNAs, miRNAs, and mRNAs.

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