Figure 3 Model for the nonsense- mediated decay. been proposed to function. Two reports have suggested that the Ltn1 protein, which is an E3 ubiquitin ligase that inter- acts with ribosomes, is required for rapid decay of the na- scent peptide (Wilson et al. 2007; Bengtson and Joazeiro 2010). In a second study, it has been suggested that Not4 promotes the ubiquitination and degradation of such na- scent peptides (Dimitrova et al. 2009), although whether this is due to differences in the reporter constructs used is yet to be resolved. In either case, the rapid degradation of the nascent and aberrant polypeptide would ensure that only proteins of the proper length are produced. The speciﬁc features of the mRNAs may affect how they become substrates for NSD or other mRNA quality control pathways. For example, while NSD mRNAs generated by poly(A) addition within the coding region require the GTPase domain of Ski7 for their degradation, non-stop mRNAs generated by a ribozyme within the coding region do not (Meaux and Van Hoof 2006). One possibility is that this difference is due to the speciﬁc loading of proteins dur- ing nuclear polyadenylation that affect NSD in the cytosol. 686 R. Parker Alternatively, it could be that mRNAs with translated poly(A) tails are subject to a hybrid type of mRNA decay that involves aspects of both NGD and NSD. This possibility is suggested by the fact that poly(A) tracts, which encode for lysine, can stall elongating ribosomes and trigger NGD (Ito-Harashima et al. 2007; Kuroha et al. 2010). An interesting area for future re- search will be to determine how speciﬁc types of mRNAs are recognized and targeted for these quality control systems. Quality control of nuclear mRNA processing Numerous quality control systems target mRNA defective in pre-mRNA splicing, polyadenylation, or mRNA export. These nuclear quality control systems prevent the function of the aberrant mRNA by triggering nuclear degradation or by nuclear export leading to cytoplasmic degradation. In addition, aberrant or unprocessed nuclear mRNAs can also be retained within the nucleus. Nuclear retention may be important both to give time for RNA processing to be completed and to allow for a kinetically disfavored nuclear degradation pathway to degrade the RNA (see below).