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. Author manuscript; available in PMC: 2010 Jan 7.
Published in final edited form as: Mol Cell. 2009 Aug 27;35(6):868–880. doi: 10.1016/j.molcel.2009.08.004

Figure 8. Model for Temporal Stepwise miRNA-Mediated Gene Silencing.

Figure 8

(i) mRNA circularization via eIF4G-PABP interaction stimulates cap-dependent translation by enhancing eIF4E’s binding to the mRNA 5′ cap structure (strong binding [Kahvejian et al., 2005]).

(ii) miRISC binds to its target site in the 3′UTR. GW182 binds to PABP, hypothetically inhibiting its interaction with eIF4G, thereby repressing cap-dependent translation by decreasing eIF4E’s binding to the 5′ cap structure (weaker binding), and sequestering the poly(A) tail into the vicinity of CAF1 and CCR4 deadenylases (illustrated by an arrow) to facilitate deadenylation of the mRNA. The interaction between CAF1/CCR4 and Ago2 is probably indirect through other proteins (depicted as question marks).