Natural amino acids do not require their native tRNAs for efficient selection by the ribosome

Philip R. Effraim, Jiangning Wang, Michael T. Englander, Josh Avins, Thomas S. Leyh, Ruben L. Gonzalez, Virginia W. Cornish

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The involvement of tRNA structural elements beyond the anticodon in aminoacyl-tRNA (aa-tRNA) selection by the ribosome has revealed that substrate recognition is considerably more complex than originally envisioned in the adaptor hypothesis. By combining recent breakthroughs in aa-tRNA synthesis and mechanistic and structural studies of protein synthesis, we have investigated whether aa-tRNA recognition further extends to the amino acid, which would explain various translation disorders exhibited by misacylated tRNAs. Contrary to expectation, we find that natural amino acids misacylated onto natural but non-native tRNAs are selected with efficiencies very similar to those of their correctly acylated counterparts. Despite this, small but reproducible differences in selection indeed demonstrate that the translational machinery is sensitive to the amino acidg-tRNA pairing. These results suggest either that the ribosome is an exquisite sensor of natural versus unnatural amino acidg-tRNA pairings and/or that aa-tRNA selection is not the primary step governing the amino acid specificity of the ribosome.

Original languageEnglish (US)
Pages (from-to)947-953
Number of pages7
JournalNature Chemical Biology
Volume5
Issue number12
DOIs
StatePublished - Dec 2009

Fingerprint

Transfer RNA
Ribosomes
Amino Acids
Anticodon

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Effraim, P. R., Wang, J., Englander, M. T., Avins, J., Leyh, T. S., Gonzalez, R. L., & Cornish, V. W. (2009). Natural amino acids do not require their native tRNAs for efficient selection by the ribosome. Nature Chemical Biology, 5(12), 947-953. https://doi.org/10.1038/nchembio.255

Natural amino acids do not require their native tRNAs for efficient selection by the ribosome. / Effraim, Philip R.; Wang, Jiangning; Englander, Michael T.; Avins, Josh; Leyh, Thomas S.; Gonzalez, Ruben L.; Cornish, Virginia W.

In: Nature Chemical Biology, Vol. 5, No. 12, 12.2009, p. 947-953.

Research output: Contribution to journalArticle

Effraim, PR, Wang, J, Englander, MT, Avins, J, Leyh, TS, Gonzalez, RL & Cornish, VW 2009, 'Natural amino acids do not require their native tRNAs for efficient selection by the ribosome', Nature Chemical Biology, vol. 5, no. 12, pp. 947-953. https://doi.org/10.1038/nchembio.255
Effraim, Philip R. ; Wang, Jiangning ; Englander, Michael T. ; Avins, Josh ; Leyh, Thomas S. ; Gonzalez, Ruben L. ; Cornish, Virginia W. / Natural amino acids do not require their native tRNAs for efficient selection by the ribosome. In: Nature Chemical Biology. 2009 ; Vol. 5, No. 12. pp. 947-953.
@article{5bec74ccf0f449c1b077ccc092201a7d,
title = "Natural amino acids do not require their native tRNAs for efficient selection by the ribosome",
abstract = "The involvement of tRNA structural elements beyond the anticodon in aminoacyl-tRNA (aa-tRNA) selection by the ribosome has revealed that substrate recognition is considerably more complex than originally envisioned in the adaptor hypothesis. By combining recent breakthroughs in aa-tRNA synthesis and mechanistic and structural studies of protein synthesis, we have investigated whether aa-tRNA recognition further extends to the amino acid, which would explain various translation disorders exhibited by misacylated tRNAs. Contrary to expectation, we find that natural amino acids misacylated onto natural but non-native tRNAs are selected with efficiencies very similar to those of their correctly acylated counterparts. Despite this, small but reproducible differences in selection indeed demonstrate that the translational machinery is sensitive to the amino acidg-tRNA pairing. These results suggest either that the ribosome is an exquisite sensor of natural versus unnatural amino acidg-tRNA pairings and/or that aa-tRNA selection is not the primary step governing the amino acid specificity of the ribosome.",
author = "Effraim, {Philip R.} and Jiangning Wang and Englander, {Michael T.} and Josh Avins and Leyh, {Thomas S.} and Gonzalez, {Ruben L.} and Cornish, {Virginia W.}",
year = "2009",
month = "12",
doi = "10.1038/nchembio.255",
language = "English (US)",
volume = "5",
pages = "947--953",
journal = "Nature Chemical Biology",
issn = "1552-4450",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Natural amino acids do not require their native tRNAs for efficient selection by the ribosome

AU - Effraim, Philip R.

AU - Wang, Jiangning

AU - Englander, Michael T.

AU - Avins, Josh

AU - Leyh, Thomas S.

AU - Gonzalez, Ruben L.

AU - Cornish, Virginia W.

PY - 2009/12

Y1 - 2009/12

N2 - The involvement of tRNA structural elements beyond the anticodon in aminoacyl-tRNA (aa-tRNA) selection by the ribosome has revealed that substrate recognition is considerably more complex than originally envisioned in the adaptor hypothesis. By combining recent breakthroughs in aa-tRNA synthesis and mechanistic and structural studies of protein synthesis, we have investigated whether aa-tRNA recognition further extends to the amino acid, which would explain various translation disorders exhibited by misacylated tRNAs. Contrary to expectation, we find that natural amino acids misacylated onto natural but non-native tRNAs are selected with efficiencies very similar to those of their correctly acylated counterparts. Despite this, small but reproducible differences in selection indeed demonstrate that the translational machinery is sensitive to the amino acidg-tRNA pairing. These results suggest either that the ribosome is an exquisite sensor of natural versus unnatural amino acidg-tRNA pairings and/or that aa-tRNA selection is not the primary step governing the amino acid specificity of the ribosome.

AB - The involvement of tRNA structural elements beyond the anticodon in aminoacyl-tRNA (aa-tRNA) selection by the ribosome has revealed that substrate recognition is considerably more complex than originally envisioned in the adaptor hypothesis. By combining recent breakthroughs in aa-tRNA synthesis and mechanistic and structural studies of protein synthesis, we have investigated whether aa-tRNA recognition further extends to the amino acid, which would explain various translation disorders exhibited by misacylated tRNAs. Contrary to expectation, we find that natural amino acids misacylated onto natural but non-native tRNAs are selected with efficiencies very similar to those of their correctly acylated counterparts. Despite this, small but reproducible differences in selection indeed demonstrate that the translational machinery is sensitive to the amino acidg-tRNA pairing. These results suggest either that the ribosome is an exquisite sensor of natural versus unnatural amino acidg-tRNA pairings and/or that aa-tRNA selection is not the primary step governing the amino acid specificity of the ribosome.

UR - http://www.scopus.com/inward/record.url?scp=73549106134&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73549106134&partnerID=8YFLogxK

U2 - 10.1038/nchembio.255

DO - 10.1038/nchembio.255

M3 - Article

VL - 5

SP - 947

EP - 953

JO - Nature Chemical Biology

JF - Nature Chemical Biology

SN - 1552-4450

IS - 12

ER -