Jose Perez-Ortin

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The yeast Saccharomyces cerevisiae and most eukaryotes carry two 5’→3’ exoribonuclease paralogues that are very similar. In yeast, they are called Xrn1, which shuttles between the nucleus and cytoplasm and executes major cytoplasmic mRNA decay, and Rat1, which carries a strong nuclear localization sequence (NLS) and localizes in the nucleus. Xrn1 is 40% homologous to Rat1 but has an extra ~500 amino acids C-terminal extension. In the cytoplasm, Xrn1 can degrade decapped mRNAs during the last round of translation by ribosomes “co-translational mRNA decay”. The division of labor between the two enzymes is still enigmatic and can serve as a paradigm for division of labor of many other paralogues. Here we show that Rat1 is capable of functioning in cytoplasmic mRNA decay, provided that Rat1 remains cytoplasmic due to its NLS disruption (cRat1). This indicates that the actual segregation of the two paralogues plays roles in their specific functions. However, segregation is not sufficient for fully complementing Xrn1 function. Specifically, cRat1 can only partially recover cell volume, mRNA stability, proliferation rate, 5’→3’ decay alterations that characterize xrn1Δ cells. In particular, co-translational decay is only little complemented by cRat1. Adding the Xrn1 C-terminal domain to Rat1 does not improve the phenotypes indicating that lack of C-terminal is not the reason for the partial complementation. Collectively, it seems that during evolution the two paralogues acquire unique features that make the division of work beneficial.