RNA Therapeutics Institute Publications
Title
Structural Basis for Translation Termination on a Pseudouridylated Stop Codon
UMMS Affiliation
RNA Therapeutics Institute; Department of Biochemistry and Molecular Pharmacology
Publication Date
2016-05-22
Document Type
Article
Disciplines
Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Genetics and Genomics | Molecular Biology | Therapeutics
Abstract
Pseudouridylation of messenger RNA emerges as an abundant modification involved in gene expression regulation. Pseudouridylation of stop codons in eukaryotic and bacterial cells results in stop-codon read through. The structural mechanism of this phenomenon is not known. Here we present a 3.1-A crystal structure of Escherichia coli release factor 1 (RF1) bound to the 70S ribosome in response to the PsiAA codon. The structure reveals that recognition of a modified stop codon does not differ from that of a canonical stop codon. Our in vitro biochemical results support this finding by yielding nearly identical rates for peptide release from E. coli ribosomes programmed with pseudouridylated and canonical stop codons. The crystal structure also brings insight into E. coli RF1-specific interactions and suggests involvement of L27 in bacterial translation termination. Our results are consistent with a mechanism in which read through of a pseudouridylated stop codon in bacteria results from increased decoding by near-cognate tRNAs (miscoding) rather than from decreased efficiency of termination.
DOI of Published Version
10.1016/j.jmb.2016.04.018
Source
J Mol Biol. 2016 May 22;428(10 Pt B):2228-36. doi: 10.1016/j.jmb.2016.04.018. Epub 2016 Apr 20. Link to article on publisher's site
Journal/Book/Conference Title
Journal of molecular biology
Related Resources
PubMed ID
27107638
Repository Citation
Svidritskiy E, Madireddy R, Korostelev AA. (2016). Structural Basis for Translation Termination on a Pseudouridylated Stop Codon. RNA Therapeutics Institute Publications. https://doi.org/10.1016/j.jmb.2016.04.018. Retrieved from https://escholarship.umassmed.edu/rti_pubs/16