Endogenous ribosomal frameshift signals operate as mRNA destabilizing elements through at least two molecular pathways in yeast.
Although first discovered in viruses, previous studies have identified operational -1 ribosomal frameshifting (-1 RF) signals in eukaryotic genomic sequences, and suggested a role in mRNA stability. Here, four yeast -1 RF signals are shown to promote significant mRNA destabilization through the nonsense mediated mRNA decay pathway (NMD), and genetic evidence is presented suggesting that they may also operate through the no-go decay pathway (NGD) as well. Yeast EST2 mRNA is highly unstable and contains up to five -1 RF signals. Ablation of the -1 RF signals or of NMD stabilizes this mRNA, and changes in -1 RF efficiency have opposing effects on the steady-state abundance of the EST2 mRNA. These results demonstrate that endogenous -1 RF signals function as mRNA destabilizing elements through at least two molecular pathways in yeast. Consistent with current evolutionary theory, phylogenetic analyses suggest that -1 RF signals are rapidly evolving cis-acting regulatory elements. Identification of high confidence -1 RF signals in ∼10% of genes in all eukaryotic genomes surveyed suggests that -1 RF is a broadly used post-transcriptional regulator of gene expression.
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Ashton T
AT
Belew
Vivek M
VM
Advani
Jonathan D
JD
Dinman
D018389:Codon, Nonsense; D019143:Evolution, Molecular; D018965:Frameshifting, Ribosomal; D020871:RNA Stability; D012331:RNA, Fungal / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D038621:Regulatory Sequences, Ribonucleic Acid; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D004718:Saccharomycetales / Q000235:genetics; D019098:Telomerase / Q000235:genetics / Q000378:metabolism
D018389:Codon, Nonsense; D012331:RNA, Fungal; D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid; D029701:Saccharomyces cerevisiae Proteins; C509185:EST2 protein, S cerevisiae; D019098:Telomerase