Fig. 4.

Mechanisms of mRNA decay. Degradation of messenger mRNA plays an essential role in regulating sustained mRNA expression. mRNA is generally degraded in the following three pathways: ① Deadenylation-dependent mRNA decay: The poly(A) tail is removed by deadenylase activity (such as CCR4, CAF1 or PARN). The LSM1-7 complex associates with the 3′-end of the mRNA transcript to induce decapping by the Dcp1–Dcp2 complex and is then degraded by exoribonuclease XRN1. Alternatively, deadenylated mRNA can be degraded by exosomes. ② Endonuclease-mediated mRNA decay: The mRNA is cleaved into two fragments, and then the fragments are degraded by XRN1 and exosomes.⁵³⁸ ③ Deadenylation-independent pathways require recruitment of the decapping machinery. RPS28B interacts with the enhancer of decapping-3 (Edc3) to engage the decapping enzyme. Subsequently, the mRNA is degraded by XRN1⁵³⁸