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Title: Structural insights into translational recoding by frameshift suppressor tRNASufJ

Abstract

The three-nucleotide mRNA reading frame is tightly regulated during translation to ensure accurate protein expression. Translation errors that lead to aberrant protein production can result from the uncoupled movement of the tRNA in either the 5' or 3' direction on mRNA. Here, we report the biochemical and structural characterization of +1 frameshift suppressor tRNASufJ, a tRNA known to decode four, instead of three, nucleotides. Frameshift suppressor tRNASufJ contains an insertion 5' to its anticodon, expanding the anticodon loop from seven to eight nucleotides. Our results indicate that the expansion of the anticodon loop of either ASLSufJ or tRNASufJ does not affect its affinity for the A site of the ribosome. Structural analyses of both ASLSufJ and ASLThr bound to the Thermus thermophilus 70S ribosome demonstrate both ASLs decode in the zero frame. Although the anticodon loop residues 34–37 are superimposable with canonical seven-nucleotide ASLs, the single C31.5 insertion between nucleotides 31 and 32 in ASLSufJ imposes a conformational change of the anticodon stem, that repositions and tilts the ASL toward the back of the A site. Further modeling analyses reveal that this tilting would cause a distortion in full-length A-site tRNASufJ during tRNA selection and possibly impede gripping of themore » anticodon stem by 16S rRNA nucleotides in the P site. Together, these data implicate tRNA distortion as a major driver of noncanonical translation events such as frameshifting.« less

Authors:
 [1];  [1];  [1];  [1];  [1]
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  1. Emory Univ., Atlanta, GA (United States). School of Medicine. Dept. of Biochemistry
Publication Date:
Research Org.:
Emory Univ., Atlanta, GA (United States)
Sponsoring Org.:
USDOE Office of Science (SC); USDOD; National Inst. of Health (NIH) (United States)
OSTI Identifier:
1182320
Grant/Contract Number:  
AC02-06CH11357; T32 GM8367; R01GM093278; RR-15301
Resource Type:
Accepted Manuscript
Journal Name:
RNA
Additional Journal Information:
Journal Volume: 20; Journal Issue: 12; Journal ID: ISSN 1355-8382
Publisher:
Cambridge University Press
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ribosome; mRNA; reading frame; anticodon stem–loop; decoding; X-ray crystal structure

Citation Formats

Fagan, Crystal E., Maehigashi, Tatsuya, Dunkle, Jack A., Miles, Stacey J., and Dunham, Christine M. Structural insights into translational recoding by frameshift suppressor tRNASufJ. United States: N. p., 2014. Web. doi:10.1261/rna.046953.114.
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Fagan, Crystal E., Maehigashi, Tatsuya, Dunkle, Jack A., Miles, Stacey J., & Dunham, Christine M. Structural insights into translational recoding by frameshift suppressor tRNASufJ. United States. https://doi.org/10.1261/rna.046953.114
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Fagan, Crystal E., Maehigashi, Tatsuya, Dunkle, Jack A., Miles, Stacey J., and Dunham, Christine M. Tue . "Structural insights into translational recoding by frameshift suppressor tRNASufJ". United States. https://doi.org/10.1261/rna.046953.114. https://www.osti.gov/servlets/purl/1182320.
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@article{osti_1182320,
title = {Structural insights into translational recoding by frameshift suppressor tRNASufJ},
author = {Fagan, Crystal E. and Maehigashi, Tatsuya and Dunkle, Jack A. and Miles, Stacey J. and Dunham, Christine M.},
abstractNote = {The three-nucleotide mRNA reading frame is tightly regulated during translation to ensure accurate protein expression. Translation errors that lead to aberrant protein production can result from the uncoupled movement of the tRNA in either the 5' or 3' direction on mRNA. Here, we report the biochemical and structural characterization of +1 frameshift suppressor tRNASufJ, a tRNA known to decode four, instead of three, nucleotides. Frameshift suppressor tRNASufJ contains an insertion 5' to its anticodon, expanding the anticodon loop from seven to eight nucleotides. Our results indicate that the expansion of the anticodon loop of either ASLSufJ or tRNASufJ does not affect its affinity for the A site of the ribosome. Structural analyses of both ASLSufJ and ASLThr bound to the Thermus thermophilus 70S ribosome demonstrate both ASLs decode in the zero frame. Although the anticodon loop residues 34–37 are superimposable with canonical seven-nucleotide ASLs, the single C31.5 insertion between nucleotides 31 and 32 in ASLSufJ imposes a conformational change of the anticodon stem, that repositions and tilts the ASL toward the back of the A site. Further modeling analyses reveal that this tilting would cause a distortion in full-length A-site tRNASufJ during tRNA selection and possibly impede gripping of the anticodon stem by 16S rRNA nucleotides in the P site. Together, these data implicate tRNA distortion as a major driver of noncanonical translation events such as frameshifting.},
doi = {10.1261/rna.046953.114},
journal = {RNA},
number = 12,
volume = 20,
place = {United States},
year = {Tue Oct 28 00:00:00 EDT 2014},
month = {Tue Oct 28 00:00:00 EDT 2014}
}
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Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1261/rna.046953.114
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Citation Metrics:
Cited by: 19 works
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Figures / Tables:

FIGURE 1 FIGURE 1: Possible models for +1 frameshifting resulting from an eight-nucleotide anticodon stem–loop. (A) The quadruplet decoding model posits that insertions in the anticodon stem–loop of a frameshift suppressor tRNA leads to a four-nucleotide anticodon capable of decoding and translocating a four-nucleotidemRNA codon (with the extra nucleotide shown in green).more » The numbering of the mRNA begins with the first position in the P site. (B) An alternative model is that the nucleotide insertion in the anticodon stem–loop causes a widening of the loop, allowing the anticodon nucleotide 34 to interact with the fourth nucleotide of the A-site codon (green; numbered as 7 inA). (C) In the P-site slippage model, normal decoding in the zero frame occurs in the A site; however, the transition into the +1 frame occurs after translocation to the P site due to a weakened interaction between the anticodon and codon.« less
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