The mitochondrial protein targeting suppressor (mts1) mutation maps to themRNA-binding domain of Npl3p and affects translation on cytoplasmic polysomes

In all eukaryotic organisms, messenger RNA (mRNA) is synthesized in the nuc leus and then exported to the cytoplasm for translation. The export reactio n requires the concerted action of a large number of protein components, in cluding a set of shuttle proteins that can exit and re-enter the nucleus th rough the nuclear pore complex. Here, we show that, in Saccharomyces cerevi siae, the shuttle protein Npl3p leaves the nuclear pore complex entirely an d continues to function in the cytoplasm. A mutation at position 219 in its RNA-binding domain leaves Npl3p lingering in the cytoplasm associated with polysomes. Yeast cells expressing the mutant Npl3(L-219S) protein show alt erations in mRNA stability that can affect protein synthesis. As a result, defects in nascent polypeptide targeting to subcellular compartments such a s the mitochondria are also suppressed.