Conservation of the RNA Transport Machineries and Their Coupling to Translation Control across Eukaryotes

Figure 1

Transport and translation repression of ASH1 mRNA in S. cerevisiae. ASH1 mRNA is synthesized in the nucleus of the mother cell. The She2p protein is loaded onto ASH1 mRNA in the nucleus. Once in the cytoplasm, the ASH1-She2p complex binds to She3p which associates with Myo4p to form the transport machinery called the “locasome”. The translation repressors Puf6p and Khd1p and Pabp1 (which is needed for localization) are thought to be also loaded onto ASH1 mRNA before nuclear export. The locasome then transports silenced ASH1 RNPs to the bud through the actin filaments. Puf6p and Khd1p block AHS1 mRNA translation during transport by different mechanisms. One of them is through the interaction of Puf6p with eIF5B and further inhibition of the recruitment of the 60S ribosomal to the mRNA. Khd1p binds eIF4G. This interaction might prevent the recruitment of the 43S pre-initiation complex (consisting of the 40S subunit, the stabilizing factors eIF3, eIF1 and eIF1A and a ternary complex composed of eIF2 bound to an initiator Met-tRNA and GTP) to the mRNA, thereby blocking translation initiation. However, the exact mechanism is not clearly understood. Once the complex is localized to the bud tip, membrane associated kinases, CK2 and Yck1p, phosphorylate Puf6p and Khd1p respectively. This produces the dissociation of the repressors from ASH1 mRNA allowing thus translation activation. Ash1p then inhibits mating-type switching only in the daughter cell.