Figure 7.

Mechanism of RIG-I signaling activation by endogenous RNA. The endogenous RIG-I ligand (eRL) is derived from the internal transcribed spacer 2 (ITS2) region of polycistronic 45S ribosomal RNA. ITS2 is excised by processing of 45S precursor rRNA to mature ribosomal RNA species and more abundant in proliferating than in resting cells. RNase treatment exposes eRL as a specific sequence derived from ITS2 region. This stimulatory RNA fragment binds GTP by internal G-quadruplexes and bears a 2′,3′-cyclic phosphate. Both these features are crucial for eRL dependent RIG-I activation.