Comparison of Xrn1 and Rat1 5′→3′ exoribonucleases in budding yeast
supports the unique role of Xrn1 in co-translational mRNA decay
Abstract
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.