Mechanism of tRNA-mediated +1 ribosomal frameshifting
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...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 44; pp. 11226 - 11231 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
30.10.2018
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Subjects | |
Online Access | Get full text |
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Summary: | 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 tRNASufA6 (a derivative of tRNAPro) 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 tRNASufA6 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 tRNASufA6 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 tRNASufA6 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 AC02-06CH11357; P41 GM103403; S10 RR029205; R01 GM093278 USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division National Inst. of General Medical Sciences Author contributions: T.M. and C.M.D. designed research; S.H., S.S., T.M., E.D.H., and C.M.D. performed research; S.H., S.S., T.M., E.D.H., J.A.D., and C.M.D. analyzed data; and S.H., S.S., T.M., E.D.H., J.A.D., and C.M.D. wrote the paper. Edited by Jonathan D. Dinman, University of Maryland, College Park, MD, and accepted by Editorial Board Member Peter B. Moore September 5, 2018 (received for review June 21, 2018) 1S.H. and S.S. contributed equally to this work. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.1809319115 |