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In Saccharomyces cerevisiae, nuclear exosome along with TRAMP and DRN selectively eliminates diverse aberrant messages. These decay apparatuses appear to operate as independent mechanisms in the nucleus. Here, using genetic and molecular approach we systematically investigate the functional relationship between exosome, TRAMP and DRN mechanisms by examining their relative contributions in the degradation of diverse classes of aberrant nuclear mRNAs generated at various phases of mRNP biogenesis. Our findings suggest that nuclear exosome in association with the TRAMP complex exclusively degrades the transcription assembly-defective mRNPs and splice-defective intron-containing pre-mRNAs, whereas nuclear exosome along with DRN solely degrades the export-defective messages. The degradation of aberrant read-through transcripts with 3′-extensions, in contrast, requires the activity of TRAMP and DRN together along with nuclear exosome function. Thus, the profile of substrate specificity of these nuclear decay machines reflects dependency of the nuclear exosome for either TRAMP or DRN function to degrade distinct nuclear mRNAs. We propose that DRN apparatus may act as a novel ancillary factor required for the nuclear exosome function to degrade specific classes of aberrant messages.