A MOUSE CYTOPLASMIC EXORIBONUCLEASE (MXRN1P) WITH PREFERENCE FOR G4 TETRAPLEX SUBSTRATES

Exoribonucleases are important enzymes for the turnover of cellular RN A species. We have isolated the first mammalian cDNA from mouse demons trated to encode a 5'-3' exoribonuclease. The structural conservation of the predicted protein and complementation data in Saccharomyces cer evisiae suggest a role in cytoplasmic mRNA turnover and pre-rRNA proce ssing similar to that of the major cytoplasmic exoribonuclease Xrn1p i n yeast. Therefore, a key component of the mRNA decay system in S. cer evisiae has been conserved in evolution from yeasts to mammals. The pu rified mouse protein (mXRN1p) exhibited a novel substrate preference f or G4 RNA tetraplex-containing substrates demonstrated in binding and hydrolysis experiments. mXRN1p is the first RNA turnover function that has been localized in the cytoplasm of mammalian cells. mXRN1p was di stributed in small granules and was highly enriched in discrete, promi nent foci. The specificity of mXRN1p suggests that RNAs containing G4 tetraplex structures may occur in vivo and may have a role in RNA turn over.