Department of Microbiology and Physiological Systems
Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Cellular and Molecular Physiology | Nucleic Acids, Nucleotides, and Nucleosides
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).
NMD, PTC, Pab1, nonsense codon, poly(A), readthrough
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Copyright 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Wu C, Roy B, He F, Yan K, Jacobson A. Poly(A)-Binding Protein Regulates the Efficiency of Translation Termination. Cell Rep. 2020 Nov 17;33(7):108399. doi: 10.1016/j.celrep.2020.108399. PMID: 33207198; PMCID: PMC7717110. Link to article on publisher's site
Wu C, Roy B, He F, Yan K, Jacobson A. (2020). Poly(A)-Binding Protein Regulates the Efficiency of Translation Termination. Open Access Publications by UMMS Authors. https://doi.org/10.1016/j.celrep.2020.108399. Retrieved from https://escholarship.umassmed.edu/oapubs/4452
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