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Title: Mechanism of tRNA-mediated +1 ribosomal frameshifting

Abstract

Accurate translation of the genetic code is critical to ensure expression of proteins with correct amino acid sequences. Certain tRNAs can cause a shift out of frame (i.e., frameshifting) due to imbalances in tRNA concentrations, lack of tRNA modifications or insertions or deletions in tRNAs (called frameshift suppressors). Here, we determined the structural basis for how frameshift-suppressor tRNA SufA6 (a derivative of tRNA Pro ) reprograms the mRNA frame to translate a 4-nt codon when bound to the bacterial ribosome. After decoding at the aminoacyl (A) site, the crystal structure of the anticodon stem-loop of tRNA SufA6 bound in the peptidyl (P) site reveals ASL conformational changes that allow for recoding into the +1 mRNA frame. Furthermore, a crystal structure of full-length tRNA SufA6 programmed in the P site shows extensive conformational rearrangements of the 30S head and body domains similar to what is observed in a translocation intermediate state containing elongation factor G (EF-G). The 30S movement positions tRNA SufA6 toward the 30S exit (E) site disrupting key 16S rRNA–mRNA interactions that typically define the mRNA frame. In summary, this tRNA-induced 30S domain change in the absence of EF-G causes the ribosome to lose its grip on the mRNAmore » and uncouples the canonical forward movement of the tRNAs during elongation.« less

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Scientific User Facilities Division; National Inst. of General Medical Sciences
OSTI Identifier:
1474210
Alternate Identifier(s):
OSTI ID: 1483075
Grant/Contract Number:  
AC02-06CH11357; P41 GM103403; S10 RR029205; R01 GM093278
Resource Type:
Journal Article: Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 115 Journal Issue: 44; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; recoding; tRNA; mRNA; ribosome; frameshift

Citation Formats

Hong, Samuel, Sunita, S., Maehigashi, Tatsuya, Hoffer, Eric D., Dunkle, Jack A., and Dunham, Christine M. Mechanism of tRNA-mediated +1 ribosomal frameshifting. United States: N. p., 2018. Web. doi:10.1073/pnas.1809319115.
Hong, Samuel, Sunita, S., Maehigashi, Tatsuya, Hoffer, Eric D., Dunkle, Jack A., & Dunham, Christine M. Mechanism of tRNA-mediated +1 ribosomal frameshifting. United States. doi:10.1073/pnas.1809319115.
Hong, Samuel, Sunita, S., Maehigashi, Tatsuya, Hoffer, Eric D., Dunkle, Jack A., and Dunham, Christine M. Thu . "Mechanism of tRNA-mediated +1 ribosomal frameshifting". United States. doi:10.1073/pnas.1809319115.
@article{osti_1474210,
title = {Mechanism of tRNA-mediated +1 ribosomal frameshifting},
author = {Hong, Samuel and Sunita, S. and Maehigashi, Tatsuya and Hoffer, Eric D. and Dunkle, Jack A. and Dunham, Christine M.},
abstractNote = {Accurate translation of the genetic code is critical to ensure expression of proteins with correct amino acid sequences. Certain tRNAs can cause a shift out of frame (i.e., frameshifting) due to imbalances in tRNA concentrations, lack of tRNA modifications or insertions or deletions in tRNAs (called frameshift suppressors). Here, we determined the structural basis for how frameshift-suppressor tRNA SufA6 (a derivative of tRNA Pro ) reprograms the mRNA frame to translate a 4-nt codon when bound to the bacterial ribosome. After decoding at the aminoacyl (A) site, the crystal structure of the anticodon stem-loop of tRNA SufA6 bound in the peptidyl (P) site reveals ASL conformational changes that allow for recoding into the +1 mRNA frame. Furthermore, a crystal structure of full-length tRNA SufA6 programmed in the P site shows extensive conformational rearrangements of the 30S head and body domains similar to what is observed in a translocation intermediate state containing elongation factor G (EF-G). The 30S movement positions tRNA SufA6 toward the 30S exit (E) site disrupting key 16S rRNA–mRNA interactions that typically define the mRNA frame. In summary, this tRNA-induced 30S domain change in the absence of EF-G causes the ribosome to lose its grip on the mRNA and uncouples the canonical forward movement of the tRNAs during elongation.},
doi = {10.1073/pnas.1809319115},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
issn = {0027-8424},
number = 44,
volume = 115,
place = {United States},
year = {2018},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1073/pnas.1809319115

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Cited by: 4 works
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