TPR and Autoimmunity: This binding mode of the 3′-anti-tag sequence of the self RNA induces minimal conformational changes of the gRAMPcrRNA-TPR-CHAT complex, including the C-helix and H-sheet conformation and the catalytic dyad H585 and C627 geometry in the CHAT protease domain (Fig. 5f, Supplementary Fig. 11, 12a), which contrasts with those induced by the 3′-flanking sequence of non-self RNA (Figs. 4d, 5f), suggesting that the TPR-CHAT protease adopts an autoinhibitory conformation upon own self RNA target binding, thereby preventing self-targeting to avoid autoimmunity.