Nrd1p identifies aberrant and natural exosomal target messages during the nuclear mRNA surveillance in Saccharomyces cerevisiae

In all eukaryotes, selective nuclear degradation of aberrant mRNAs by nuclear exosome and its cofactors TRAMP, and CTEXT contribute to the fidelity of the gene expression pipeline. In the model eukaryote, Saccharomyces cerevisiae, the Nrd1p-Nab3p-Sen1p (NNS) complex, previously known to be involved in the transcription termination and matured 39-end formation of vast majority of non-coding and several coding RNAs, is demonstrated to universally participate in the nuclear decay of various kinds of faulty messages in this study. Consistently, nrd1-1/nrd1-2 mutant cells display impairment of the decay of all kinds of aberrant mRNAs, like the yeast mutants deficient in Rrp41p, Rrp6p, and Rrp4p. nrd1deltaCID mutation (consisting of Nrd1p lacking its CID domain thereby abrogating its interaction with RNAPII) however, abolishes the decay of aberrant messages generated during early phases of mRNP biogenesis (transcription elongation, splicing and 39-end maturation) without affecting the decay rate of the export-defective mRNAs. Mutation in the 39-end processing factor, Pcf11p, in contrast, displayed a selective abolition of the decay of the aberrant mRNAs, generated at the late phase of mRNP biogenesis (export-defective mRNAs) without influencing the faulty messages spawned in the early phase of mRNP biogenesis. Co-transcriptional recruitment of Nrd1p onto the faulty messages, which relies on RNAPII during transcription elongation and on Pcf11p post transcription, is vital for the exosomal decay of aberrant mRNAs, as Nrd1p deposition on the export-defective messages led to the Rrp6p recruitment and eventually, their decay. Thus, presence of the Nrd1p mark on aberrant mRNAs appears rate-limiting for the distinction of the aberrant messages from their normal functional counterparts.