Conserved microRNA editing in mammalian evolution, development and disease.

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• Mammalian microRNAs (miRNAs) undergo adenosine-to-inosine RNA editing, altering target specificity and expression.
• The evolutionary history and conservation of miRNA editing across species remain largely unexplored.

Purpose of the Study:

• To investigate the evolutionary conservation of microRNA editing events across diverse species.
• To understand the functional implications of conserved miRNA editing in mammalian transcriptomes.

Main Methods:

• Comparative genomic analysis of miRNA sequences across various mammalian and non-mammalian species.
• Identification and characterization of conserved site-specific miRNA editing events.
• Analysis of miRNA editing frequencies in different tissues, ages, and disease states.

Main Results:

• Deep conservation of site-specific miRNA editing events, with some dating back to the common ancestor of mammals and bony fishes (450 million years ago).
• Evidence of recent miRNA family expansion in placental mammals, with editing linked to target mRNA expression changes during primate development and aging.
• Variations in miRNA editing frequencies across tissues (neural vs. others), age (older vs. younger), and disease states (healthy vs. tumors), suggesting a link to cell proliferation rates.

Conclusions:

• Site-specific miRNA editing is an evolutionarily conserved mechanism that broadens the functional repertoire of mammalian miRNA transcriptomes.
• MicroRNAs are significantly overrepresented among conserved RNA editing targets, despite miRNA editing being less common than long RNA editing.