Beyond the pro forma demonstration that À1 RF signals can decrease cellular mRNA abundance, it is important to begin to understand the biological function of this phenomenon. As a first step in this direction, we showed that silently mutating the slippery sites in 5 predicted À1 RF signals within a full-length clone of EST2 significantly stabilized its encoded mRNA ( Figure 5B) . Similarly, abrogation of NMD stabilized this message, while changes in À1 RF efficiency inversely correlated with EST2 steady-state mRNA abundance. Est2p is the reverse transcriptase subunit of the telomerase holoenzyme (21) . Interestingly, prior studies have demonstrated that this mRNA, along with other mRNAs encoding proteins having telomere-associated functions, are stabilized in NMD À yeast cells (33, 37) . Analysis of the Programmed Ribosomal Frameshift Database (http:// prfdb.umd.edu/) reveals that, along with the other four putative À1 RF signals in the EST2 mRNA, the mRNAs encoding Est1p, Stn1p, Cdc13p and Orc5p, all components or regulators of telomerase that are stabilized in NMD À cells, also contain high confidence À1 RF signals (Supplementary Figure S2 ). In addition, the EST3 mRNA contains a +1 PRF signal (46) . Intriguingly, telomerase is limiting in cells: while a yeast cell contains 64 chromosome ends, there are only $29 telomerase molecules per cell, and telomerase is preferentially recruited to short telomeres (47) . Additionally, Tbf1p is a telobox containing general regulatory factor that binds to TTAGGG repeats within subtelomeric anti-silencing regions (48) . Intriguingly, ablation of NMD (49) or overexpression of single components of telomerase-associated proteins, i.e. the TEL1 RNA, Est2p, Stn1p or Cdc13p resulted in changes in telomere length (47, 50, 51) .