TRIM21 undergoes phase separation dependent CC domain to regulate autophagy

Tripartite motif (TRIM) family proteins as E3-ligases participate in various biological processes. TRIM21, as the first autoantibody protein, has been found to be associated with autophagy. However, the role of TRIM21 engaging in autophagy is still unclear. In this study, TRIM21 forms significate puncta in the cytoplasm and undergoes liquid-liquid phase separation in vitro. Furthermore, we identify phase separation of the coiled-coil (CC) domain is essential for autophagosome to mediate autophagy-related protein recruited. These findings show that phase separation of the CC domain of TRIM21 promotes autophagosome to impact cell fate. •TRIM21 undergoes liquid-liquid phase separation in vivo and vitro.•Coiled-coil (CC) domain of TRIM21 driving condense formation.•Phase separation of TRIM21 contributes to autophagy independent p62 nuclear formation.