Multiple G-quartet structures in pre-edited mRNAs suggest evolutionary driving force for RNA editing in trypanosomes

Area of Science:

• Molecular Biology
• Parasitology
• Genetics

Background:

• Mitochondrial RNA editing in African trypanosomes is a complex process involving U-nucleotide insertion/deletion.
• The origin and biological significance of this extensive RNA editing remain largely unknown.

Purpose of the Study:

• To investigate the structural features of pre-edited mitochondrial mRNAs in African trypanosomes.
• To explore the potential role of these features in RNA editing, genome replication, and transcription.

Main Methods:

• Bioinformatic analysis to identify structural elements in pre-edited mRNAs.
• Correlation analysis between G-quadruplex structures and guide RNA abundance.
• Postulation of DNA/RNA hybrid G-quadruplex formation.

Main Results:

• Discovery of clustered G-rich motifs forming G-quadruplexes (GQ) in pre-edited mRNAs.
• Identification of 27 GQ structures across different pre-mRNAs.
• Positive correlation observed between guide RNA abundance and GQ element positioning.

Conclusions:

• G-rich sequences forming GQ structures may be recognized and resolved by RNA editing.
• Formation of DNA/RNA hybrid G-quadruplexes (HQ) between transcripts and mtDNA could serve as replication initiation/transcription termination sites.
• RNA editing, transcription, and replication appear to be interconnected processes that may have coevolved with the parasite's life cycle and single mitochondrion.