Nat. Struct. Mol. Biol., published online 9 September 2012; doi:10.1038/nsmb.2381
The 5′ end of mRNA in eukaryotes is modified—or 'capped'—with a methylated guanine nucleotide to protect the mRNA from impromptu degradation. Chang et al. report that the yeast enzyme Ydr370C (renamed Dxo1), which is weakly homologous to the recently discovered RNA pyrophosphohydrolase and decapping enzyme Rai1, may be responsible for detecting and degrading incompletely capped mRNAs that are mistakenly exported into the yeast cytoplasm. The authors solved the X-ray crystal structure of Dxo1 and assessed the biochemical properties of the two enzymes. Rai1 was previously shown to act as a pyrophosphohydrolase, removing a pyrophosphate group from uncapped RNA that had a triphosphate group on its 5′ end, and as a decapping enzyme, completely removing the 5′ cap of a capped, unmethylated RNA. Dxo1 was also able to remove the 5′ cap of a capped, unmethylated RNA, but it was not able to catalyze the pyrophosphohydrolase reaction. In addition, Dxo1 was then able to act as a 5′-3′ exoribonuclease, degrading the uncapped piece of RNA. The authors showed that knocking out both Dxo1 and Rai1 in yeast led to an increase in incompletely 5′-capped mRNA under normal growth conditions. They believe that these two enzymes—Rai1 in the nucleus and Dxo1 in the cytoplasm—are key members of a previously undetected surveillance system that is responsible for degrading incompletely capped mRNAs.
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