29 Destabilization of Nonsense-containing Transcripts in Saccharomyces cerevisiae

Abstract

DESTABILIZATION OF ABERRANT mRNAS CONTRIBUTES TO THE ACCURACY OF GENE EXPRESSION
Gene expression is a highly accurate process in which the final products, i.e., proteins, contain no more than one incorrect amino acid per 10,000 inserted (Kurland 1992; Yarus 1992). This high level of accuracy underwrites nature’s genetic systems and ensures that even very large polypeptides will be functional. Several cooperative and concurrently operating mechanisms are responsible for maintaining fidelity in the flow of genetic information, including those that monitor the integrity of RNA synthesis and processing, tRNA aminoacylation, codon:anticodon pairing, and peptide elongation (Yarus 1992; Chin and Pyle 1995; Freist et al. 1996; Jeon and Agarwal 1996; Ibba and Soll 1999; Yoshizawa et al. 1999). Because these mechanisms are incapable of rectifying errors attributable to mutations, other processes have evolved that rid the cell of improperly folded proteins and mRNAs that lack complete open reading frames (He et al. 1993; Cui et al. 1995; Wickner et al. 1999). The latter transcripts are typically those containing premature termination (or “nonsense”) codons, and the process which ensures that these mRNAs do not accumulate as substrates for the translation apparatus has been dubbed nonsense-mediated mRNA decay (NMD), or mRNA surveillance (Peltz et al. 1993a, 1994; Pulak and Anderson 1993).

Although shown to operate in a broad spectrum of eukaryotic organisms (for a discussion of this phenomenon in mammals, see Chapter 30), NMD has been most extensively studied in the yeast Saccharomyces cerevisiae, largely because of the facility of genetic analyses (Losson and...