Fig. 8: Model of CCR4-NOT-mediated deadenylation and its inhibition by RNF219.
From: RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation
The non-catalytic NOT2/3 and NOT9 modules facilitate access of substrate poly(A) RNA to the catalytic NOT6/NOT7 module and thereby promote sequence-independent mRNA deadenylation. RNF219 interacts with the NOT9 module via a SLiM (depicted as a helical peptide) within its C-terminal low-complexity region. RNF219 may occupy the RNA interaction surface on NOT9 and hinder access of poly(A) RNA to the catalytic module. Alternatively, RNF219 may reduce the catalytic activity of CCR4 or CAF1, given the proximity of the NOT9 and the catalytic module. Inhibition of CCR4-NOT-mediated deadenylation by RNF219 occurs in the absence of its N-terminal RING domain and thus, is independent of its E3 ligase activity. The N-terminal RING domain of RNF219 is dispensable for stabilization of short-lived mRNAs yet required for stabilization of long-lived mRNAs.
