Translation of circular RNAs.

Area of Science:

• Molecular Biology
• Genomics
• Biochemistry

Background:

• Circular RNAs (circRNAs) are a class of covalently closed RNA molecules found in eukaryotes.
• RNA sequencing reveals millions of human circRNA isoforms, significantly outnumbering known messenger RNA (mRNA) isoforms.
• CircRNAs are primarily located in the cytosol, exhibiting stability and functional roles, including sequestering microRNAs and RNA-binding proteins.

Purpose of the Study:

• To review the growing evidence for circRNA translation into proteins.
• To explore the diverse cap-independent mechanisms driving circRNA translation.
• To highlight the implications of circRNA-derived proteins in disease.

Main Methods:

• Analysis of RNA sequencing data to identify circRNA abundance and isoforms.
• Review of literature on circRNA biogenesis, including backsplicing and intronic element influence.
• Examination of established and emerging cap-independent translation mechanisms (e.g., IRES, m6A, A-to-I editing, eIF4A3 interaction).

Main Results:

• CircRNAs are translated into proteins via multiple cap-independent pathways.
• Translation is favored under conditions like cancer, yielding shorter proteins than mRNA-encoded counterparts.
• These circRNA-derived proteins may possess novel functions relevant to disease pathogenesis.

Conclusions:

• Circular RNAs are not merely non-coding transcripts but can generate functional proteins.
• The translation of circRNAs represents a significant expansion of the proteome.
• Understanding circRNA translation is crucial for disease research and therapeutic development.