Figure 5.

Intermediates in 3′–5′ degradation of histone mRNA. The histone mRNP associated with SLBP, 3′hExo and TUT7 (figure 1a) is the actively translating form of histone mRNA. The proposed initial step in histone mRNA degradation is loss of efficient translation termination (possibly by an unknown modification of SLBP). This results in binding of Upf1 and Smg1, phosphorylation of Upf1 and subsequent weakening of the SLBP/SL interaction, allowing 3′hExo to initiate degradation into the stemloop. The U-tails added in the stem bind Lsm1–7, which can also bind directly to SLBP and 3′hExo through the C-terminal tail of Lsm4. This intermediate accumulates but is resolved by loss of SLBP and 3′hExo, followed by loss of Upf1, resulting in the recruitment of the exosome and rapid degradation until the exosome encounters the ribosome bound to the stop codon, resulting in the formation of a uridylated intermediate. Subsequent degradation can occur either (or both) 5′–3′ as a result of continued exonucleolytic degradation and/or decapping of the mRNA and 5′–3′ degradation.