Figure 5 Model for non-stop decay. initiation and untranslated mRNAs in yeast tend to be rapidly deadenylated and decapped (Muhlrad et al. 1995). Pre-mRNAs can also be degraded after the formation of the lariat intermediate. In this case, when the lariat in- termediate is stuck—either due to mutations in the intron (Hilleren and Parker 2003; Mayas et al. 2010) or to errors in 59 splice site choice or stochastic events in endogenous genes (Y. Harigaya and R. Parker, unpublished data)—the 39 intron–exon lariat is debranched, exported to the cyto- plasm, and degraded by Xrn1 or the cytoplasmic exosome. Moreover, the Prp43 ATPase is required for this discard path- way, presumably to facilitate spliceosome disassembly, thereby allowing export (Mayas et al. 2010). Unspliced pre-mRNAs from reporter mRNAs can also be retained at the nuclear pore by the Mlp1 and Mlp2 proteins (Galy et al. 2004), although this system appears to part of a more general quality control system for mRNA export that is not limited to pre-mRNAs (Vinciguerra et al. 2005). Quality control of 39 end generation: Multiple types of mutations lead to defects in mRNA 39 end generation and polyadenylation. For example, mutations in proteins re- quired for recognition of the polyadenylation site or the poly(A) polymerase Pap1 can alter the site of 39 end forma- tion and, in the case of pap1 alleles, lead to the production of unadenylated mRNAs (Patel and Butler 1992; Mandart and Parker 1995). Similarly, defects in mRNA export factors 688 R. Parker or in the Tho complex, which couples transcription and mRNP assembly, lead to hyperadenylation of mRNAs, per- haps due to a failure to recycle mRNP proteins to the nu- cleus (Hilleren and Parker 2001; Jensen et al. 2001; Libri et al. 2002). Several studies suggest that yeast mRNAs with aberrant 39 ends are retained at the site of transcription (Hilleren et al. 2001; Jensen et al. 2001; Thomsen et al. 2003). More- over, this retention appears to be due to the absence of a proper poly(A) tail since mRNAs where the 39 end is gen- erated by a ribozyme are often retained (Libri et al. 2002) unless a poly(A) tract is encoded 59 of the site of ribozyme cleavage (Dower et al. 2004). The retention of aberrant mRNAs with aberrant ends requires the 39 to 59 exonuclease activity of the nuclear exosome and is reduced in rrp6Δ strains, or by mutations in the exonuclease active sites of Rrp6 or Dis3/Rrp44 (Hilleren et al. 2001; Libri et al. 2002; Thomsen et al. 2003; Assenholt et al. 2008). The role of the exosome sug- gested that these aberrant mRNAs might be degraded in the nucleus by the nuclear exosome. However, in some cases the actual levels of mRNAs do not increase in the rrp6Δ strains, although the mRNAs are no longer nuclear retained, suggesting that the role of the exosome might be to allow retention, and not degrade, the mRNAs (Hilleren et al. 2001). In contrast, in other studies it has been sug- gested that the exosome degrades these mRNAs since, in