Figure 4 Model for no-go decay. Examples of nuclear retention of aberrant mRNAs include the retention of mRNAs with defects in polyadenylation (Hilleren et al. 2001; Jensen et al. 2001). Interestingly, these aberrant RNAs are retained in the vicinity of the gene (Thomsen et al. 2003), which has the potential to have feedback effects on transcription. Quality control of pre-mRNA splicing: Several RNA degra- dation systems contribute to degrading unspliced or mis- spliced pre-mRNAs (Figure 6). For the Rps22b and Rpl18a pre-mRNAs, the intron contains a cleavage site for the yeast RNAseIII enzyme, Rnt1, and endonuclease cleavage within the intron reduces the pool of both pre-mRNA and the ex- cised intron (Danin-Kreiselman et al. 2003). This reaction appears to occur in the nucleus due to Rnt1 being concen- trated in the nucleus, and the observation that the pre- mRNA cleavage products are degraded by the nuclear Rrp6 and Rat1 nucleases (Danin-Kreiselman et al. 2003). Nuclear pre-mRNA degradation has also been proposed for pre-mRNAs that fail to enter splicing or are trapped as lariat intermediates (Bousquet-Antonelli et al. 2000). In contrast to nuclear degradation, multiple experiments suggest that unspliced pre-mRNA are exported to the cytoplasm and degraded. This was ﬁrst suggested by the observation that the CYH2 pre-mRNA was exported to the cytoplasm and degraded by NMD (He et al. 1993). Genome-wide analysis has shown that a number of pre-mRNAs with weak splicing signals are exported to the cytosol and then degraded by NMD (Sayani et al. 2008). In addition, in strains with defective splicing machinery, NMD is seen to degrade pre-mRNAs from even more genes (Kawashima et al. 2009). Bioinformatics analysis suggests that this is an effective way to monitor introns since intron sequences contain an overrepre- sentation of translation termination signals and would tend to channel pre-mRNAs that enter translation into NMD (reviewed in Egecioglu and Chanfreau 2011). NMD would also be expected to degrade errors in splice site choice that lead to frameshifting during translation and thereby to premature translation termination. Unspliced pre-mRNAs can also be degraded in the cyto- plasm independently of NMD (Hilleren and Parker 2003), perhaps because the retained intron represses translation RNA Decay in Yeast 687