Figure 6 Mechanisms of degradation for unspliced pre-mRNAs. strains defective in the THO complex, the 39 end of some mRNAs is reduced compared to the 59 end, implying that some mRNAs have been degraded in a 39 to 59 direction (Libri et al. 2002). In principle, mRNAs generated in mutants with defects in 39-end formation might be subject to three different fates and that population studies might give misleading results due to different populations behaving in different ways. For example, in export or THO mutant strains a sub- set of the transcripts is produced with normal 39-end gen- eration and poly(A) tails, and these appear to undergo normal export, deadenylation, and cytoplasmic decapping (Hilleren and Parker 2001; Libri et al. 2002). A second population of mRNAs are those that are produced with either hypo- or hyperadenylated 39 ends. Strikingly, the observable population of both hyperadenylated and hypo- adenylated mRNAs is quite stable, suggesting that these mRNAs are retained within the nucleus and are stable in that state (Mandart and Parker 1995; Hilleren and Parker 2001; Rougemaille et al. 2007). Finally, it may be that there is a pool of mRNAs that are recognized as aberrant and subjected to extremely rapid degradation (Rougemaille et al. 2007). Since these mRNAs are proposed to degrade very rapidly, it would not be possible to measure their decay rates from steady state as the steady-state pool will consist only of mRNAs that have escaped this rapid degradation. An important issue in future work is determin- ing if such rapid degradation does occur and determining its mechanism. Intergenic, Intragenic, Promoter-Associated, and Antisense RNAs From genome-wide analysis it is now clear that yeast cells produce numerous untraditional transcripts. Such transcripts include intergenic and intragenic transcripts (referred to as cryptic unstable transcripts, stable unannotated transcripts, or Xrn1-sensitive unstable transcripts); antisense RNAs; transcripts associated with or overlapping promoter regions (referred to as promoter-associated RNAs); and RNAs from heterochromatin, including telomeric, centromere, and rRNA spacer regions (Olivas et al. 1997; Wyers et al. 2005; Houseley et al. 2007, 2008; Luke et al. 2008). These transcripts can be produced from bidirectional transcription from promoters of known genes (Neil et al. 2009; Xu et al. 2009) or from distinct promoters (Rhee and Pugh 2012) and have been suggested to have a variety of functions. For example, some anti- sense RNAs, or their act of transcription, can play a role in modulating the expression of the corresponding sense gene via histone modiﬁcation (Camblong et al. 2007; Berretta et al. 2008; Houseley et al. 2008; Geisler et al. 2012). At least in the case of the GAL1 mRNA, the deg- radation of an antisense RNA appears to be required for efﬁcient induction of the corresponding sense transcript RNA Decay in Yeast 689