FIGURE 10-27 Pathways for degradation Of eukaryotic mRNAS. (a) In the most common pathway of mRNA degradation, the deadenylation-dependent pathway, the poly(A) tail is progressively shortened by a deadenylase complex until it reaches a length of 20 or fewer A residues, at which point the interaction between PABPC1 and the remaining poly(A) is destabilized, leading to weakened interactions between the 5′ cap and translation initiation factors (see Figure 5-23). The deadenylated mRNA then may either (1) be decapped by the DCP1/DCP2 deadenylation complex and degraded by XRN1, a 5′→3′ exonuclease, or (2) be degraded by 3′→5′ exonucleases in cytoplasmic exosomes. (b) Other mRNAs are decapped before they are deadenylated and then degraded by the XRN1 5′→3′ exonuclease. In the example shown from yeast, an RNA-binding protein Rps28B binds a sequence in the 3’-UTR of its own mRNA, which then interacts with Edc3 (enhancer of decapping 3). Edc3 then recruits the DCP1/2 decapping enzyme to the mRNA, auto regulating expression of Rps28B. (c) Some mRNAs are cleaved internally by an endonuclease and the fragments degraded by a cytoplasmic exosome and the XRN1 exonuclease. See N. L. Garneau, J. Wilusz, and C. J. Wilusz, 2007, Nat. Rev. Mol. Cell Biol. 8:113.