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The Evolution of Imprinted microRNAs and Their RNA Targets

David Haig1, Avantika Mainieri1

  • 1Department of Organismic and Evolutionary Biology, Harvard University, 26 Oxford Street, Cambridge, MA 02138, USA.

Genes
|September 9, 2020
PubMed

Insights

Imprinted microRNAs regulate gene expression. When microRNAs target messenger RNAs, the messenger RNA may evolve to evade or accommodate this regulation, impacting genomic evolution.

Area of Science:

  • Genomics
  • Evolutionary Biology
  • Molecular Biology

Background:

  • Mammalian genomes feature numerous imprinted microRNAs (miRNAs).
  • Interactions between imprinted miRNAs and unimprinted messenger RNAs (mRNAs) can lead to varied fitness outcomes for the encoding loci.
  • mRNA sequence evolution can be constrained by functional requirements, influencing its response to miRNA regulation.

Purpose of the Study:

  • To explore the evolutionary dynamics of imprinted miRNA-mRNA interactions.
  • To illustrate how mRNA sequences adapt to regulation by imprinted miRNAs.

Main Methods:

  • Analysis of evolutionary responses in mRNA sequences to miRNA targeting.
  • Case studies using primate C19MC and mouse C2MC miRNA clusters.
  • Examination of the 3' untranslated region (UTR) of the PTEN gene as a miRNA target.

Main Results:

  • mRNA sequences may evolve to evade miRNA regulation via target site changes.
  • When evasion is not possible due to functional constraints, mRNA evolves to accommodate miRNA regulation.
  • The imprinted C19MC and C2MC miRNA clusters target the 3' UTR of PTEN, a gene involved in growth and metabolism.

Conclusions:

  • Evolutionary pressures shape the interaction between imprinted miRNAs and their mRNA targets.
  • mRNA accommodation of imprinted miRNA regulation is a significant evolutionary pathway, particularly for functionally constrained genes.
  • The PTEN gene's 3' UTR is a key target site for primate and mouse imprinted miRNAs, highlighting conserved regulatory mechanisms.
Keywords:
C14MCC19MCC2MCIGF2PTENevolutionimprintingmiRNA

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