Uncovering translation roadblocks during the development of a synthetic tRNA

Prabhakar, Arjun; Krahn, Natalie; Zhang, Jingji; Vargas-Rodriguez, Oscar; Krupkin, Miri; Fu, Ziao; Acosta-Reyes, Francisco J.; Ge, Xueliang; Choi, Junhong; Crnković, Ana; Ehrenberg, Måns; Puglisi, Elisabetta Viani; Söll, Dieter; Puglisi, Joseph

doi:10.1093/nar/gkac576

Title: Uncovering translation roadblocks during the development of a synthetic tRNA

Abstract

Ribosomes are remarkable in their malleability to accept diverse aminoacyl-tRNA substrates from both the same organism and other organisms or domains of life. This is a critical feature of the ribosome that allows the use of orthogonal translation systems for genetic code expansion. Optimization of these orthogonal translation systems generally involves focusing on the compatibility of the tRNA, aminoacyl-tRNA synthetase, and a non-canonical amino acid with each other. As we expand the diversity of tRNAs used to include non-canonical structures, the question arises as to the tRNA suitability on the ribosome. Specifically, we investigated the ribosomal translation of allo-tRNA^UTu1, a uniquely shaped (9/3) tRNA exploited for site-specific selenocysteine insertion, using single-molecule fluorescence. With this technique we identified ribosomal disassembly occurring from translocation of allo-tRNA^UTu1 from the A to the P site. Using cryo-EM to capture the tRNA on the ribosome, we pinpointed a distinct tertiary interaction preventing fluid translocation. Through a single nucleotide mutation, we disrupted this tertiary interaction and relieved the translation roadblock. With the continued diversification of genetic code expansion, our work highlights a targeted approach to optimize translation by distinct tRNAs as they move through the ribosome.

Authors:

Prabhakar, Arjun ^[1]; Krahn, Natalie ^[2]; Zhang, Jingji ^[1]; Vargas-Rodriguez, Oscar ^[2]; Krupkin, Miri ^[1]; Fu, Ziao ^[3]; Acosta-Reyes, Francisco J. ^[3]; Ge, Xueliang ^[4]; Choi, Junhong ^[1]; Crnković, Ana ^[2]; Ehrenberg, Måns ^[4]; Puglisi, Elisabetta Viani ^[1];

^[2];

^[1]

Stanford Univ., CA (United States)
Yale Univ., New Haven, CT (United States)
Columbia Univ., New York, NY (United States)
Uppsala Univ. (Sweden)

Publication Date:: Wed Jul 27 00:00:00 EDT 2022

Research Org.:: Yale Univ., New Haven, CT (United States)

Sponsoring Org.:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); Cystic Fibrosis Foundation; Knut and Alice Wallenberg Foundation

OSTI Identifier:: 1904746

Grant/Contract Number:: FG02-98ER20311; R35 GM122560; R35 GM122560-05S1; GM51266; AI15046; T32-GM008294; PUGLIS20G0; KAW 2016.0488

Resource Type:: Accepted Manuscript

Journal Name:: Nucleic Acids Research

Additional Journal Information:: Journal Volume: 50; Journal Issue: 18; Journal ID: ISSN 0305-1048

Publisher:: Oxford University Press

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; Biochemistry & Molecular Biology

Citation Formats


                    Prabhakar, Arjun, Krahn, Natalie, Zhang, Jingji, Vargas-Rodriguez, Oscar, Krupkin, Miri, Fu, Ziao, Acosta-Reyes, Francisco J., Ge, Xueliang, Choi, Junhong, Crnković, Ana, Ehrenberg, Måns, Puglisi, Elisabetta Viani, Söll, Dieter, and Puglisi, Joseph. Uncovering translation roadblocks during the development of a synthetic tRNA.  United States: N. p., 2022. 
Web.  doi:10.1093/nar/gkac576.

Copy to clipboard


                    Prabhakar, Arjun, Krahn, Natalie, Zhang, Jingji, Vargas-Rodriguez, Oscar, Krupkin, Miri, Fu, Ziao, Acosta-Reyes, Francisco J., Ge, Xueliang, Choi, Junhong, Crnković, Ana, Ehrenberg, Måns, Puglisi, Elisabetta Viani, Söll, Dieter, & Puglisi, Joseph. Uncovering translation roadblocks during the development of a synthetic tRNA.  United States.  https://doi.org/10.1093/nar/gkac576

Copy to clipboard


                    Prabhakar, Arjun, Krahn, Natalie, Zhang, Jingji, Vargas-Rodriguez, Oscar, Krupkin, Miri, Fu, Ziao, Acosta-Reyes, Francisco J., Ge, Xueliang, Choi, Junhong, Crnković, Ana, Ehrenberg, Måns, Puglisi, Elisabetta Viani, Söll, Dieter, and Puglisi, Joseph. Wed .  
"Uncovering translation roadblocks during the development of a synthetic tRNA".  United States.  https://doi.org/10.1093/nar/gkac576.  https://www.osti.gov/servlets/purl/1904746.

Copy to clipboard


                    
@article{osti_1904746,

  title        = {Uncovering translation roadblocks during the development of a synthetic tRNA},

  author       = {Prabhakar, Arjun and Krahn, Natalie and Zhang, Jingji and Vargas-Rodriguez, Oscar and Krupkin, Miri and Fu, Ziao and Acosta-Reyes, Francisco J. and Ge, Xueliang and Choi, Junhong and Crnković, Ana and Ehrenberg, Måns and Puglisi, Elisabetta Viani and Söll, Dieter and Puglisi, Joseph},

  abstractNote = {Ribosomes are remarkable in their malleability to accept diverse aminoacyl-tRNA substrates from both the same organism and other organisms or domains of life. This is a critical feature of the ribosome that allows the use of orthogonal translation systems for genetic code expansion. Optimization of these orthogonal translation systems generally involves focusing on the compatibility of the tRNA, aminoacyl-tRNA synthetase, and a non-canonical amino acid with each other. As we expand the diversity of tRNAs used to include non-canonical structures, the question arises as to the tRNA suitability on the ribosome. Specifically, we investigated the ribosomal translation of allo-tRNAUTu1, a uniquely shaped (9/3) tRNA exploited for site-specific selenocysteine insertion, using single-molecule fluorescence. With this technique we identified ribosomal disassembly occurring from translocation of allo-tRNAUTu1 from the A to the P site. Using cryo-EM to capture the tRNA on the ribosome, we pinpointed a distinct tertiary interaction preventing fluid translocation. Through a single nucleotide mutation, we disrupted this tertiary interaction and relieved the translation roadblock. With the continued diversification of genetic code expansion, our work highlights a targeted approach to optimize translation by distinct tRNAs as they move through the ribosome.},

  doi          = {10.1093/nar/gkac576},

  journal      = {Nucleic Acids Research},

  number       = 18,

  volume       = 50,

  place        = {United States},

  year         = {Wed Jul 27 00:00:00 EDT 2022},

  month        = {Wed Jul 27 00:00:00 EDT 2022}

}

Copy to clipboard

Journal Article:

Free Publicly Available Full Text

Accepted Manuscript (DOE)

Publisher's Version of Record

https://doi.org/10.1093/nar/gkac576

Other availability

Search WorldCat to find libraries that may hold this journal

Save / Share:

Export Metadata

Save to My Library

Works referenced in this record:

Naturally Occurring tRNAs With Non-canonical Structures
journal, October 2020

Krahn, Natalie; Fischer, Jonathan T.; Söll, Dieter
Frontiers in Microbiology, Vol. 11
DOI: 10.3389/fmicb.2020.596914

An extended structural signature for the tRNA anticodon loop
journal, March 2001

Auffinger, Pascal; Westhof, Eric
RNA, Vol. 7, Issue 3
DOI: 10.1017/S1355838201002382

Structure of an adenine˙cytosine base pair in DNA and its implications for mismatch repair
journal, April 1986

Hunter, William N.; Brown, Tom; Anand, Naveen N.
Nature, Vol. 320, Issue 6062
DOI: 10.1038/320552a0

Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome
journal, February 2010

Neumann, Heinz; Wang, Kaihang; Davis, Lloyd
Nature, Vol. 464, Issue 7287
DOI: 10.1038/nature08817

Systematic Evolution and Study of UAGN Decoding tRNAs in a Genomically Recoded Bacteria
journal, February 2016

Wang, Nanxi; Shang, Xin; Cerny, Ronald
Scientific Reports, Vol. 6, Issue 1
DOI: 10.1038/srep21898

An innate twist between Crick’s wobble and Watson-Crick base pairs
journal, July 2013

Ananth, Prakash; Goldsmith, Gunaseelan; Yathindra, Narayanarao
RNA, Vol. 19, Issue 8
DOI: 10.1261/rna.036905.112

Solution conformation of an RNA hairpin loop
journal, May 1990

Puglisi, Joseph D.; Wyatt, Jacqueline R.; Tinoco, Ignacio
Biochemistry, Vol. 29, Issue 17
DOI: 10.1021/bi00469a026

Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome
journal, April 2009

Voorhees, Rebecca M.; Weixlbaumer, Albert; Loakes, David
Nature Structural & Molecular Biology, Vol. 16, Issue 5
DOI: 10.1038/nsmb.1577

Multiplex suppression of four quadruplet codons via tRNA directed evolution
journal, September 2021

DeBenedictis, Erika A.; Carver, Gavriela D.; Chung, Christina Z.
Nature Communications, Vol. 12, Issue 1
DOI: 10.1038/s41467-021-25948-y

Recognition and selection of tRNA in translation
journal, November 2004

Rodnina, Marina V.; Gromadski, Kirill B.; Kothe, Ute
FEBS Letters, Vol. 579, Issue 4
DOI: 10.1016/j.febslet.2004.11.048

Optimization of speed and accuracy of decoding in translation
journal, September 2010

Wohlgemuth, Ingo; Pohl, Corinna; Rodnina, Marina V.
The EMBO Journal, Vol. 29, Issue 21
DOI: 10.1038/emboj.2010.229

The energy landscape of −1 ribosomal frameshifting
journal, January 2020

Choi, Junhong; O’Loughlin, Sinéad; Atkins, John F.
Science Advances, Vol. 6, Issue 1
DOI: 10.1126/sciadv.aax6969

Post-termination Ribosome Intermediate Acts as the Gateway to Ribosome Recycling
journal, July 2017

Prabhakar, Arjun; Capece, Mark C.; Petrov, Alexey
Cell Reports, Vol. 20, Issue 1
DOI: 10.1016/j.celrep.2017.06.028

High-throughput platform for real-time monitoring of biological processes by multicolor single-molecule fluorescence
journal, December 2013

Chen, J.; Dalal, R. V.; Petrov, A. N.
Proceedings of the National Academy of Sciences, Vol. 111, Issue 2
DOI: 10.1073/pnas.1315735111

Highly reproductive Escherichia coli cells with no specific assignment to the UAG codon
journal, May 2015

Mukai, Takahito; Hoshi, Hiroko; Ohtake, Kazumasa
Scientific Reports, Vol. 5, Issue 1
DOI: 10.1038/srep09699

Compilation of tRNA sequences and sequences of tRNA genes
journal, January 1998

Sprinzl, Mathias; Horn, Carsten; Brown, Melissa
Nucleic Acids Research, Vol. 26, Issue 1, p. 148-153
DOI: 10.1093/nar/26.1.148

Expanding the Genetic Code of Escherichia coli
journal, April 2001

Wang, L.; Brock, A.; Herberich, B.
Science, Vol. 292, Issue 5516, p. 498-500
DOI: 10.1126/science.1060077

What recent ribosome structures have revealed about the mechanism of translation
journal, October 2009

Schmeing, T. Martin; Ramakrishnan, V.
Nature, Vol. 461, Issue 7268
DOI: 10.1038/nature08403

Intein-based Design Expands Diversity of Selenocysteine Reporters
journal, April 2022

Chung, Christina Z.; Krahn, Natalie; Crnković, Ana
Journal of Molecular Biology, Vol. 434, Issue 8
DOI: 10.1016/j.jmb.2021.167199

Design and Synthesis of FRET-Mediated Multicolor and Photoswitchable Fluorescent Polymer Nanoparticles with Tunable Emission Properties
journal, March 2012

Chen, Jian; Zhang, Peisheng; Fang, Gang
The Journal of Physical Chemistry B, Vol. 116, Issue 14
DOI: 10.1021/jp2110659

An Oxygen Scavenging System for Improvement of Dye Stability in Single-Molecule Fluorescence Experiments
journal, March 2008

Aitken, Colin Echeverría; Marshall, R. Andrew; Puglisi, Joseph D.
Biophysical Journal, Vol. 94, Issue 5
DOI: 10.1529/biophysj.107.117689

A Facile Method for Producing Selenocysteine-Containing Proteins
journal, May 2018

Mukai, Takahito; Sevostyanova, Anastasia; Suzuki, Tateki
Angewandte Chemie International Edition, Vol. 57, Issue 24
DOI: 10.1002/anie.201713215

Insights into genome recoding from the mechanism of a classic +1-frameshifting tRNA
journal, January 2021

Gamper, Howard; Li, Haixing; Masuda, Isao
Nature Communications, Vol. 12, Issue 1
DOI: 10.1038/s41467-020-20373-z

Nascent peptides that block protein synthesis in bacteria
journal, February 2013

Woolstenhulme, Christopher J.; Parajuli, Shankar; Healey, David W.
Proceedings of the National Academy of Sciences, Vol. 110, Issue 10
DOI: 10.1073/pnas.1219536110

Capturing Transition States for tRNA Hybrid-State Formation in the Ribosome
journal, August 2016

Nguyen, Kien; Whitford, Paul C.
The Journal of Physical Chemistry B, Vol. 120, Issue 34
DOI: 10.1021/acs.jpcb.6b04476

Evolving tRNA^Sec for Efficient Canonical Incorporation of Selenocysteine
journal, December 2014

Thyer, Ross; Robotham, Scott A.; Brodbelt, Jennifer S.
Journal of the American Chemical Society, Vol. 137, Issue 1, p. 46-49
DOI: 10.1021/ja510695g

The A-site Finger in 23 S rRNA Acts as a Functional Attenuator for Translocation
journal, September 2006

Komoda, Taeko; Sato, Neuza S.; Phelps, Steven S.
Journal of Biological Chemistry, Vol. 281, Issue 43
DOI: 10.1074/jbc.M607058200

How the Ribosomal A-Site Finger Can Lead to tRNA Species-Dependent Dynamics
journal, March 2017

Nguyen, Kien; Yang, Huan; Whitford, Paul C.
The Journal of Physical Chemistry B, Vol. 121, Issue 13
DOI: 10.1021/acs.jpcb.7b01072

A synthetic tRNA for EF-Tu mediated selenocysteine incorporation in vivo and in vitro
journal, July 2015

Miller, Corwin; Bröcker, Markus J.; Prat, Laure
FEBS Letters, Vol. 589, Issue 17, p. 2194-2199
DOI: 10.1016/j.febslet.2015.06.039

Reprogramming the Genetic Code: From Triplet to Quadruplet Codes
journal, January 2012

Wang, Kaihang; Schmied, Wolfgang H.; Chin, Jason W.
Angewandte Chemie International Edition, Vol. 51, Issue 10
DOI: 10.1002/anie.201105016

Measuring the tolerance of the genetic code to altered codon size
journal, March 2022

DeBenedictis, Erika Alden; Söll, Dieter; Esvelt, Kevin M.
eLife, Vol. 11
DOI: 10.7554/eLife.76941

Substrate-Induced Formation of Ribosomal Decoding Center for Accurate and Rapid Genetic Code Translation
journal, May 2018

Pavlov, Michael Y.; Ehrenberg, Måns
Annual Review of Biophysics, Vol. 47, Issue 1
DOI: 10.1146/annurev-biophys-060414-034148

How the ribosome hands the A-site tRNA to the P site during EF-G-catalyzed translocation
journal, September 2014

Zhou, J.; Lancaster, L.; Donohue, J. P.
Science, Vol. 345, Issue 6201
DOI: 10.1126/science.1255030

Pyrrolysyl-tRNA synthetase: An ordinary enzyme but an outstanding genetic code expansion tool
journal, June 2014

Wan, Wei; Tharp, Jeffery M.; Liu, Wenshe R.
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1844, Issue 6
DOI: 10.1016/j.bbapap.2014.03.002

Rewiring Translation for Elongation Factor Tu-Dependent Selenocysteine Incorporation
journal, November 2012

Aldag, Caroline; Bröcker, Markus J.; Hohn, Michael J.
Angewandte Chemie International Edition, Vol. 52, Issue 5, p. 1441-1445
DOI: 10.1002/anie.201207567

The pathway to GTPase activation of elongation factor SelB on the ribosome
journal, November 2016

Fischer, Niels; Neumann, Piotr; Bock, Lars V.
Nature, Vol. 540, Issue 7631, p. 80-85
DOI: 10.1038/nature20560

The C-A mismatch base pair and the single-strand terminus in theE. coliinitiator tRNA^fMetacceptor stem adopt unusual conformations
journal, April 2000

Zuleeg, Tilman; Vogtherr, Martin; Schübel, Harald
FEBS Letters, Vol. 472, Issue 2-3
DOI: 10.1016/S0014-5793(00)01459-9

The role of tRNA as a molecular spring in decoding, accommodation, and peptidyl transfer
journal, November 2004

Frank, Joachim; Sengupta, Jayati; Gao, Haixiao
FEBS Letters, Vol. 579, Issue 4
DOI: 10.1016/j.febslet.2004.10.105

Decoding of tandem quadruplets by adjacent tRNAs with eight-base anticodon loops
journal, September 2000

Moore, B.
Nucleic Acids Research, Vol. 28, Issue 18
DOI: 10.1093/nar/28.18.3615

An expanded genetic code with a functional quadruplet codon
journal, May 2004

Anderson, J. C.; Wu, N.; Santoro, S. W.
Proceedings of the National Academy of Sciences, Vol. 101, Issue 20, p. 7566-7571
DOI: 10.1073/pnas.0401517101

Similar Records in DOE PAGES and OSTI.GOV collections:

The tRNA discriminator base defines the mutual orthogonality of two distinct pyrrolysyl-tRNA synthetase/tRNAPyl pairs in the same organism

Journal Article Zhang, Haolin ; Gong, Xuemei ; Zhao, Qianqian ; ... - Nucleic Acids Research

Site-specific incorporation of distinct non-canonical amino acids into proteins via genetic code expansion requires mutually orthogonal aminoacyl-tRNA synthetase/tRNA pairs. Pyrrolysyl-tRNA synthetase (PylRS)/tRNA^Pyl pairs are ideal for genetic code expansion and have been extensively engineered for developing mutually orthogonal pairs. Here, we identify two novel wild-type PylRS/tRNA^Pyl pairs simultaneously present in the deep-rooted extremely halophilic euryarchaeal methanogen Candidatus Methanohalarchaeum thermophilum HMET1, and show that both pairs are functional in the model halophilic archaeon Haloferax volcanii. These pairs consist of two different PylRS enzymes and two distinct tRNAs with dissimilar discriminator bases. Surprisingly, these two PylRS/tRNA^Pyl pairs display mutual orthogonality enabled bymore »« less
https://doi.org/10.1093/nar/gkac271
Pyrrolysyl-tRNA Synthetase, an Aminoacyl-tRNA Synthetase for Genetic Code Expansion

Journal Article Crnkovic, Ana ; Suzuki, Tateki ; Soll, Dieter ; ... - Croatica Chemica Acta

Genetic code expansion (GCE) has become a central topic of synthetic biology. GCE relies on engineered aminoacyl-tRNA synthetases (aaRSs) and a cognate tRNA species to allow codon reassignment by co-translational insertion of non-canonical amino acids (ncAAs) into proteins. Introduction of such amino acids increases the chemical diversity of recombinant proteins endowing them with novel properties. Such proteins serve in sophisticated biochemical and biophysical studies both in vitro and in vivo, they may become unique biomaterials or therapeutic agents, and they afford metabolic dependence of genetically modified organisms for biocontainment purposes. In the Methanosarcinaceae the incorporation of the 22nd genetically encodedmore »« less
Cited by 18
https://doi.org/10.5562/cca2825

Full Text Available
Indirect Routes to Aminoacyl-tRNA: The Diversity of Prokaryotic Cysteine Encoding Systems

Journal Article Mukai, Takahito ; Amikura, Kazuaki ; Fu, Xian ; ... - Frontiers in Genetics

Universally present aminoacyl-tRNA synthetases (aaRSs) stringently recognize their cognate tRNAs and acylate them with one of the proteinogenic amino acids. However, some organisms possess aaRSs that deviate from the accurate translation of the genetic code and exhibit relaxed specificity toward their tRNA and/or amino acid substrates. Typically, these aaRSs are part of an indirect pathway in which multiple enzymes participate in the formation of the correct aminoacyl-tRNA product. The indirect cysteine (Cys)-tRNA pathway, originally thought to be restricted to methanogenic archaea, uses the unique O -phosphoseryl-tRNA synthetase (SepRS), which acylates the non-proteinogenic amino acid O -phosphoserine (Sep) onto tRNA ^Cysmore »« less
https://doi.org/10.3389/fgene.2021.794509
Versatility of Synthetic tRNAs in Genetic Code Expansion

Journal Article Hoffman, Kyle ; Crnković, Ana ; Söll, Dieter - Genes

Transfer RNA (tRNA) is a dynamic molecule used by all forms of life as a key component of the translation apparatus. Each tRNA is highly processed, structured, and modified, to accurately deliver amino acids to the ribosome for protein synthesis. The tRNA molecule is a critical component in synthetic biology methods for the synthesis of proteins designed to contain non-canonical amino acids (ncAAs). The multiple interactions and maturation requirements of a tRNA pose engineering challenges, but also offer tunable features. Major advances in the field of genetic code expansion have repeatedly demonstrated the central importance of suppressor tRNAs for efficientmore »« less
Cited by 9
https://doi.org/10.3390/genes9110537

Full Text Available
Mechanism of tRNA-mediated +1 ribosomal frameshifting

Journal Article Hong, Samuel ; Sunita, S. ; Maehigashi, Tatsuya ; ... - Proceedings of the National Academy of Sciences of the United States of America

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 themore »« less
Cited by 29
https://doi.org/10.1073/pnas.1809319115

Similar Records

Title: Uncovering translation roadblocks during the development of a synthetic tRNA

Abstract

Citation Formats

Naturally Occurring tRNAs With Non-canonical Structures journal, October 2020

An extended structural signature for the tRNA anticodon loop journal, March 2001

Structure of an adenine˙cytosine base pair in DNA and its implications for mismatch repair journal, April 1986

Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome journal, February 2010

Systematic Evolution and Study of UAGN Decoding tRNAs in a Genomically Recoded Bacteria journal, February 2016

An innate twist between Crick’s wobble and Watson-Crick base pairs journal, July 2013

Solution conformation of an RNA hairpin loop journal, May 1990

Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome journal, April 2009

Multiplex suppression of four quadruplet codons via tRNA directed evolution journal, September 2021

Recognition and selection of tRNA in translation journal, November 2004

Optimization of speed and accuracy of decoding in translation journal, September 2010

The energy landscape of −1 ribosomal frameshifting journal, January 2020

Post-termination Ribosome Intermediate Acts as the Gateway to Ribosome Recycling journal, July 2017

High-throughput platform for real-time monitoring of biological processes by multicolor single-molecule fluorescence journal, December 2013

Highly reproductive Escherichia coli cells with no specific assignment to the UAG codon journal, May 2015

Compilation of tRNA sequences and sequences of tRNA genes journal, January 1998

Expanding the Genetic Code of Escherichia coli journal, April 2001

What recent ribosome structures have revealed about the mechanism of translation journal, October 2009

Intein-based Design Expands Diversity of Selenocysteine Reporters journal, April 2022

Design and Synthesis of FRET-Mediated Multicolor and Photoswitchable Fluorescent Polymer Nanoparticles with Tunable Emission Properties journal, March 2012

An Oxygen Scavenging System for Improvement of Dye Stability in Single-Molecule Fluorescence Experiments journal, March 2008

A Facile Method for Producing Selenocysteine-Containing Proteins journal, May 2018

Insights into genome recoding from the mechanism of a classic +1-frameshifting tRNA journal, January 2021

Nascent peptides that block protein synthesis in bacteria journal, February 2013

Capturing Transition States for tRNA Hybrid-State Formation in the Ribosome journal, August 2016

Evolving tRNASec for Efficient Canonical Incorporation of Selenocysteine journal, December 2014

The A-site Finger in 23 S rRNA Acts as a Functional Attenuator for Translocation journal, September 2006

How the Ribosomal A-Site Finger Can Lead to tRNA Species-Dependent Dynamics journal, March 2017

A synthetic tRNA for EF-Tu mediated selenocysteine incorporation in vivo and in vitro journal, July 2015

Reprogramming the Genetic Code: From Triplet to Quadruplet Codes journal, January 2012

Measuring the tolerance of the genetic code to altered codon size journal, March 2022

Substrate-Induced Formation of Ribosomal Decoding Center for Accurate and Rapid Genetic Code Translation journal, May 2018

How the ribosome hands the A-site tRNA to the P site during EF-G-catalyzed translocation journal, September 2014

Pyrrolysyl-tRNA synthetase: An ordinary enzyme but an outstanding genetic code expansion tool journal, June 2014

Rewiring Translation for Elongation Factor Tu-Dependent Selenocysteine Incorporation journal, November 2012

The pathway to GTPase activation of elongation factor SelB on the ribosome journal, November 2016

The C-A mismatch base pair and the single-strand terminus in theE. coliinitiator tRNAfMetacceptor stem adopt unusual conformations journal, April 2000

The role of tRNA as a molecular spring in decoding, accommodation, and peptidyl transfer journal, November 2004

Decoding of tandem quadruplets by adjacent tRNAs with eight-base anticodon loops journal, September 2000

An expanded genetic code with a functional quadruplet codon journal, May 2004

Naturally Occurring tRNAs With Non-canonical Structures
journal, October 2020

An extended structural signature for the tRNA anticodon loop
journal, March 2001

Structure of an adenine˙cytosine base pair in DNA and its implications for mismatch repair
journal, April 1986

Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome
journal, February 2010

Systematic Evolution and Study of UAGN Decoding tRNAs in a Genomically Recoded Bacteria
journal, February 2016

An innate twist between Crick’s wobble and Watson-Crick base pairs
journal, July 2013

Solution conformation of an RNA hairpin loop
journal, May 1990

Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome
journal, April 2009

Multiplex suppression of four quadruplet codons via tRNA directed evolution
journal, September 2021

Recognition and selection of tRNA in translation
journal, November 2004

Optimization of speed and accuracy of decoding in translation
journal, September 2010

The energy landscape of −1 ribosomal frameshifting
journal, January 2020

Post-termination Ribosome Intermediate Acts as the Gateway to Ribosome Recycling
journal, July 2017

High-throughput platform for real-time monitoring of biological processes by multicolor single-molecule fluorescence
journal, December 2013

Highly reproductive Escherichia coli cells with no specific assignment to the UAG codon
journal, May 2015

Compilation of tRNA sequences and sequences of tRNA genes
journal, January 1998

Expanding the Genetic Code of Escherichia coli
journal, April 2001

What recent ribosome structures have revealed about the mechanism of translation
journal, October 2009

Intein-based Design Expands Diversity of Selenocysteine Reporters
journal, April 2022

Design and Synthesis of FRET-Mediated Multicolor and Photoswitchable Fluorescent Polymer Nanoparticles with Tunable Emission Properties
journal, March 2012

An Oxygen Scavenging System for Improvement of Dye Stability in Single-Molecule Fluorescence Experiments
journal, March 2008

A Facile Method for Producing Selenocysteine-Containing Proteins
journal, May 2018

Insights into genome recoding from the mechanism of a classic +1-frameshifting tRNA
journal, January 2021

Nascent peptides that block protein synthesis in bacteria
journal, February 2013

Capturing Transition States for tRNA Hybrid-State Formation in the Ribosome
journal, August 2016

Evolving tRNA^Sec for Efficient Canonical Incorporation of Selenocysteine
journal, December 2014

The A-site Finger in 23 S rRNA Acts as a Functional Attenuator for Translocation
journal, September 2006

How the Ribosomal A-Site Finger Can Lead to tRNA Species-Dependent Dynamics
journal, March 2017

A synthetic tRNA for EF-Tu mediated selenocysteine incorporation in vivo and in vitro
journal, July 2015

Reprogramming the Genetic Code: From Triplet to Quadruplet Codes
journal, January 2012

Measuring the tolerance of the genetic code to altered codon size
journal, March 2022

Substrate-Induced Formation of Ribosomal Decoding Center for Accurate and Rapid Genetic Code Translation
journal, May 2018

How the ribosome hands the A-site tRNA to the P site during EF-G-catalyzed translocation
journal, September 2014

Pyrrolysyl-tRNA synthetase: An ordinary enzyme but an outstanding genetic code expansion tool
journal, June 2014

Rewiring Translation for Elongation Factor Tu-Dependent Selenocysteine Incorporation
journal, November 2012

The pathway to GTPase activation of elongation factor SelB on the ribosome
journal, November 2016

The C-A mismatch base pair and the single-strand terminus in theE. coliinitiator tRNA^fMetacceptor stem adopt unusual conformations
journal, April 2000

The role of tRNA as a molecular spring in decoding, accommodation, and peptidyl transfer
journal, November 2004

Decoding of tandem quadruplets by adjacent tRNAs with eight-base anticodon loops
journal, September 2000

An expanded genetic code with a functional quadruplet codon
journal, May 2004