As an important mode of suppressing gene expression, messenger RNAs containing 
an AU-rich element (ARE) in the 3' untranslated region are rapidly degraded in 
the cytoplasm. ARE-mediated mRNA decay (AMD) is initiated by deadenylation, and 
in vitro studies have indicated that subsequent degradation occurs in the 3'-5' 
direction through a complex of exonucleases termed the exosome. An alternative 
pathway of mRNA degradation occurs at processing bodies, cytoplasmic foci that 
contain decapping enzymes, the 5'-3' exonuclease Xrn1 and the Lsm1-7 heptamer. 
To determine which of the two pathways is important for AMD in live cells, we 
targeted components of both pathways using short interfering RNA in human HT1080 
cells. We show that Xrn1 and Lsm1 are essential for AMD. On the other side, out 
of three exosome components tested, only knockdown of PmScl-75 caused a strong 
inhibition of AMD. Our results show that mammalian cells, similar to yeast, 
require the 5'-3' Xrn1 pathway to degrade ARE-mRNAs.