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MicroRNA 3' ends shorten during adolescent brain maturation

Kristen T Thomas1, Anaïs Vermare1, Suzannah O Egleston1

  • 1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, United States.

Frontiers in Molecular Neuroscience
|May 1, 2023
PubMed

Insights

MicroRNA (miRNA) 3' end shortening increases with age during brain maturation. This age-associated miRNA modification is conserved across species and impacts gene expression in the developing brain.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • MicroRNA (miRNA) dysregulation is linked to psychiatric disorders.
  • MiRNA dynamics during adolescent and early adult brain development are not well understood.
  • This developmental period is critical as psychiatric symptoms often emerge.

Purpose of the Study:

  • To investigate miRNA and mRNA target dynamics during postnatal brain maturation in mice.
  • To explore the functional consequences of age-associated miRNA modifications.
  • To determine if miRNA 3' end shortening is conserved in human brain development.

Main Methods:

  • RNA sequencing of cortex and hippocampus in mice across developmental stages (early-, mid-, late-adolescent, adult).
  • Quantitative proteomics using tandem mass tag mass spectrometry (TMT-MS) on mouse cortex.
  • Bioinformatic analysis of miRNA and mRNA target correlations and comparison with existing human datasets.

Main Results:

  • Approximately 25% of miRNAs showed age-dependent 3' end shortening due to increased trimming and decreased U tailing.
  • Specific isomiRs of miR-338-3p increased up to 10-fold in the brain during adolescence.
  • Shortened miRNAs showed stronger correlations with age-varying mRNA targets compared to miRNAs with stable 3' ends.
  • Age-associated miRNA 3' shortening was confirmed in human brain data.

Conclusions:

  • Age-associated miRNA 3' shortening is a conserved feature of postnatal brain maturation.
  • This modification influences the regulatory relationship between miRNAs and their mRNA targets during development.
  • Understanding these dynamics may provide insights into the neurobiological basis of psychiatric disorders.
Keywords:
RNA-seqadolescencebrain maturationisomiRsmiR-338-3pmicroRNAneurodevelopmentquantitative proteomics

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