Sensing Self and Foreign Circular RNAs by Intron Identity

Area of Science:

• Immunology
• Molecular Biology
• Virology

Background:

• Circular RNAs (circRNAs) are RNA molecules with a unique head-to-tail structure.
• Their functions, particularly in the immune system, remain largely unexplored.

Purpose of the Study:

• To investigate the role of circRNAs in innate immunity and viral protection.
• To identify the mechanisms by which circRNAs are recognized by the host immune system.

Main Methods:

• Transfection of in vitro generated circRNAs into mammalian cells.
• Assessing the induction of innate immunity genes and protection against viral infection.
• Investigating the role of the RIG-I sensor and circRNA structure in immune activation.

Main Results:

• Transfected circRNAs potently induced innate immunity genes and protected against viral infection.
• The Retinoic acid-inducible gene I (RIG-I) sensor is essential for recognizing foreign circRNAs.
• Immune activation by circRNAs is independent of sequence or structure, but dependent on the programming intron, distinguishing self from non-self.

Conclusions:

• CircRNAs are recognized by the innate immune system, specifically via RIG-I.
• Introns play a critical role in circRNA biogenesis and self-nonself discrimination.
• This study reveals a novel mechanism for immune surveillance involving circRNAs and their introns.