A significant fraction of mRNAs are degraded by the nuclear exosome in normal 
cells. Here, we studied where and when these exosome target mRNAs are sorted 
away from properly exported ones in the cells. We show that upon exosome 
inactivation, polyA RNAs are apparently accumulated in nuclear foci that are 
distinct from nuclear speckles (NSs), and provide several lines of evidence 
supporting that these polyA RNAs mainly correspond to accumulating exosome 
target mRNAs. These results suggest that exosomal mRNA degradation mostly occurs 
outside of NSs. In support of this possibility, targeting exosome target mRNAs 
to NSs stabilizes them by preventing exosomal degradation. Furthermore, 
inhibiting mRNA release from NSs does not attenuate exosomal degradation in 
normal cells, and results in polyA RNA accumulation both inside and outside of 
NSs in exosome inactivated cells, suggesting that passage through NSs is not 
required for sorting mRNAs for degradation or export. Indeed, exosome target 
mRNAs that normally do not enter NSs are exported upon exosome inactivation. 
Together, our data suggest that exosome target mRNAs are mainly degraded in the 
nucleoplasm before entering NSs and rapid removal of these mRNAs is important 
for preventing their nuclear export.