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. Author manuscript; available in PMC: 2024 Jan 1.
Published in final edited form as: Trends Biochem Sci. 2022 Jul 7:S0968-0004(22)00146-3. doi: 10.1016/j.tibs.2022.06.005

Figure 5. Current model of TDMD.

Figure 5.

The ZSWIM8 E3 ubiquitin ligase recognizes and ubiquitylates AGO engaged with a TDMD target. Extensive 3′-pairing of the miRNA to the TDMD target exposes the 3′ end of the miRNA, enabling tailing by terminal nucleotidyl transferases. Ubiquitylated AGO is degraded by the proteasome and subsequent release of the miRNA leads to its degradation by unknown cytoplasmic RNases. The target transcript is recycled for another round of TDMD. CUL3: Cullin 3; Ub: Ubiquitin. Figure created with Biorender.com.