Adenosine-to-inosine RNA editing shapes transcriptome diversity in primates

Area of Science:

• Genomics
• Neuroscience
• Molecular Biology

Background:

• Human and chimpanzee genomes are highly similar, yet humans exhibit superior cognitive abilities.
• Adenosine-to-inosine (A-to-I) RNA editing is a prevalent transcriptome modification, with higher levels observed in humans compared to nonprimates, especially within primate-specific Alu sequences.
• The global RNA editing levels in nonhuman primates remain largely uncharacterized.

Purpose of the Study:

• To investigate and compare the global RNA editing levels in Alu sequences across humans, chimpanzees, and rhesus monkeys.
• To explore the potential role of A-to-I RNA editing in the development of higher brain functions in humans.

Main Methods:

• Sequencing of transcribed Alu sequences in humans, chimpanzees, and rhesus monkeys.
• Comparative analysis of RNA editing levels in brain tissues.
• Identification and analysis of species-specific Alu insertions and their association with neuronal genes.

Main Results:

• The average RNA editing level in analyzed transcripts is higher in the human brain compared to nonhuman primates, even in unmodified genomic Alu structures.
• Correlated editing patterns were observed for specific adenosine sites within Alu sequences.
• Post-human-chimpanzee split, new editable, species-specific Alu insertions are significantly enriched in genes associated with neuronal functions and neurological diseases.

Conclusions:

• Enhanced A-to-I RNA editing in the human brain, particularly within Alu sequences, may contribute to the evolution of higher cognitive functions.
• Combinatorial editing significantly expands the transcriptome repertoire.
• Alu editing, potentially shaped by natural selection, could function as an alternative information system using an A/I binary code.