RT Journal Article SR Electronic T1 Nonsense suppression position effect implicates poly(A)-binding protein in the regulation of translation termination JF bioRxiv FD Cold Spring Harbor Laboratory SP 793158 DO 10.1101/793158 A1 Chan Wu A1 Bijoyita Roy A1 Feng He A1 Allan Jacobson YR 2019 UL http://biorxiv.org/content/early/2019/10/06/793158.abstract AB Readthrough of translation termination codons, also known as nonsense suppression, is a relatively inefficient process mediated by ribosomal A site recognition and insertion of near-cognate tRNAs. Multiple factors influence readthrough efficiency, including nonsense codon specificity and context. To determine whether nonsense codon position in a gene influences the extent of readthrough, we generated a series of LUC nonsense alleles and quantitated both readthrough and termination efficiencies at each nonsense codon in yeast cells lacking nonsense-mediated mRNA decay (NMD) activity. Readthrough efficiency for premature termination codons (PTCs) manifested a marked dependence on PTC proximity to the mRNA 3’-end, decreasing progressively across the LUC ORF but increasing with 3’-UTR lengthening. These effects were eliminated, and translation termination efficiency decreased considerably, in cells harboring pab1 mutations. Our results support a critical role for poly(A)-binding protein in the regulation of translation termination and suggest that inefficient termination is the trigger for NMD.