Poly(A)-Binding Protein Regulates the Efficiency of Translation Termination

Multiple factors influence translation termination efficiency, including nonsense codon identity and immediate context. To determine whether the relative position of a nonsense codon within an open reading frame (ORF) influences termination efficiency, we quantitate the production of prematurely terminated and/or readthrough polypeptides from 26 nonsense alleles of 3 genes expressed in yeast. The accumulation of premature termination products and the extent of readthrough for the respective premature termination codons (PTCs) manifest a marked dependence on PTC proximity to the mRNA 3′ end. Premature termination products increase in relative abundance, whereas readthrough efficiencies decrease progressively across different ORFs, and readthrough efficiencies for a PTC increase in response to 3′ UTR lengthening. These effects are eliminated and overall translation termination efficiency decreases considerably in cells harboring pab1 mutations. Our results support a critical role for poly(A)-binding protein in the regulation of translation termination and also suggest that inefficient termination is a trigger for nonsense-mediated mRNA decay (NMD). [Display omitted] •Premature translational termination manifests position effects in yeast mRNAs•Termination increases and readthrough decreases as stop codons approach the ORF 3′ end•Stop codon proximity to 3′ poly(A)-binding protein regulates termination efficiency•Positional variation and termination dependence on Pab1 support an NMD faux-UTR model Premature termination codons (PTCs) trigger translational termination and can promote mRNA decay. Wu et al. insert PTCs at multiple locations in yeast genes and find that their termination efficiencies increase with proximity to ORF 3′ ends and that this positional effect on termination is modulated through mRNA-associated poly(A)-binding protein.