Translation of CircRNAs

Area of Science:

• Molecular Biology
• Genetics
• RNA Biology

Background:

• Circular RNAs (circRNAs) are prevalent and conserved RNA molecules with largely undetermined functions.
• The potential for circRNAs to be translated into proteins has been a subject of ongoing investigation.

Purpose of the Study:

• To investigate whether a subset of circular RNAs (circRNAs) can be translated into proteins in vivo.
• To characterize the mechanisms and regulatory factors involved in circRNA translation.

Main Methods:

• Ribosome footprinting in fly heads to identify circRNAs associated with translating ribosomes.
• In vivo and in vitro translation assays to assess the translational capacity of circRNAs.
• Mass spectrometry to detect circRNA-encoded proteins.

Main Results:

• A subset of circRNAs was found to be associated with translating ribosomes (ribo-circRNAs).
• Many ribo-circRNAs utilize the host mRNA's start codon and possess conserved termination codons.
• A circRNA from the muscleblind locus was shown to encode a detectable protein.
• UTRs of ribo-circRNAs (cUTRs) facilitate cap-independent translation.
• Starvation and FOXO were implicated in regulating a circMbl isoform's translation.

Conclusions:

• This study provides compelling evidence for the in vivo translation of circRNAs.
• CircRNA translation represents a previously unrecognized layer of gene activity and protein production.
• The findings open new avenues for understanding gene regulation and function through circRNAs.