MicroRNA 3' ends shorten during adolescent brain maturation

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.