title: Yeast telomere maintenance is globally controlled by programmed ribosomal frameshifting and the nonsense-mediated mRNA decay pathway.
abstract: We have previously shown that ~10% of all eukaryotic mRNAs contain potential programmed -1 ribosomal frameshifting (-1 PRF) signals and that some function as mRNA destabilizing elements through the Nonsense-Mediated mRNA Decay (NMD) pathway by directing translating ribosomes to premature termination codons. Here, the connection between -1 PRF, NMD and telomere end maintenance are explored. Functional -1 PRF signals were identified in the mRNAs encoding two components of yeast telomerase, EST1 and EST2, and in mRNAs encoding proteins involved in recruiting telomerase to chromosome ends, STN1 and CDC13. All of these elements responded to mutants and drugs previously known to stimulate or inhibit -1 PRF, further supporting the hypothesis that they promote -1 PRF through the canonical mechanism. All affected the steady-state abundance of a reporter mRNA and the wide range of -1 PRF efficiencies promoted by these elements enabled the determination of an inverse logarithmic relationship between -1 PRF efficiency and mRNA accumulation. Steady-state abundances of the endogenous EST1, EST2, STN1 and CDC13 mRNAs were similarly inversely proportional to changes in -1 PRF efficiency promoted by mutants and drugs, supporting the hypothesis that expression of these genes is post-transcriptionally controlled by -1 PRF under native conditions. Overexpression of EST2 by ablation of -1 PRF signals or inhibition of NMD promoted formation of shorter telomeres and accumulation of large budded cells at the G2/M boundary. A model  is presented describing how limitation and maintenance of correct stoichiometries of telomerase components by -1 PRF is used to maintain yeast telomere length.
authors.affiliation: Department of Cell Biology and Molecular Genetics; University of Maryland; College Park MD, USA.
authors.forename: Vivek M
authors.initials: VM
authors.lastname: Advani
authors.affiliation: Department of Cell Biology and Molecular Genetics; University of Maryland; College Park MD, USA.
authors.forename: Ashton T
authors.initials: AT
authors.lastname: Belew
authors.affiliation: Department of Cell Biology and Molecular Genetics; University of Maryland; College Park MD, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Dinman
keywords: Nonsense-mediated decay; cell cycle; frameshifting; mRNA; ribosome; telomerase