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Organocatalytic asymmetric α-C–H functionalization of alkyl amines

The catalytic activation of alkyl amines as α-nitrogen carbanions is challenging. Now the activation of N-arylidene-protected alkyl amines as carbanions by chiral ammonium organocatalysis for asymmetric conjugate addition and the Mannich reaction is reported, affording chiral α,α-dialkyl amines.

Tianran Deng
Xiang-Lei Han
Li Deng
Research03 Oct 2024
Nature Catalysis

Volume: 7, P: 1076-1085
Orthogonal use of a human tRNA synthetase active site to achieve multifunctionality

tRNA synthetases (RSs) have been implicated in functions beyond tRNA synthesis, and human TrpRS has been implicated in inhibiting angiogenesis. Tryptophan residues implicated in homotypic interactions on VE-cadherin are now shown to bind the active site of a naturally truncated TrpRS, indicating how this enzyme has been repurposed.

Quansheng Zhou
Mili Kapoor
Xiang-Lei Yang
Research13 Dec 2009
Nature Structural & Molecular Biology

Volume: 17, P: 57-61
Correction: Corrigendum: Impaired protein translation in Drosophila models for Charcot–Marie–Tooth neuropathy caused by mutant tRNA synthetases

Sven Niehues
Julia Bussmann
Erik Storkebaum
Amendments and CorrectionsOpen Access21 Jan 2016
Nature Communications

Volume: 7, P: 1
Correction: Corrigendum: CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase

Weiwei He
Ge Bai
Xiang-Lei Yang
Amendments and Corrections20 Jan 2016
Nature

Volume: 532, P: 402
Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy

Tyrosyl-tRNA synthetase (TyrRS) is a translation factor and predominantly cytoplasmic, but can also be found in the nucleus. Here authors show using a fly model of Charcot-Marie-Tooth (CMT) disease that nuclear localization of mutant TyrRS contributes to the CMT-like phenotype.

Sven Bervoets
Na Wei
Xiang-Lei Yang
ResearchOpen Access06 Nov 2019
Nature Communications

Volume: 10, P: 1-14
Author Correction: Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase

Bingyi Chen
Siting Luo
Huihao Zhou
Amendments and CorrectionsOpen Access29 Apr 2021
Nature Communications

Volume: 12, P: 1
Author Correction: The selective tRNA aminoacylation mechanism based on a single G•U pair

Masahiro Naganuma
Shun-ichi Sekine
Shigeyuki Yokoyama
Amendments and Corrections20 Nov 2018
Nature

Volume: 564, P: E37
ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase

The crystal structure of prolyl tRNA synthetase simultaneously bound to its substrate ATP and its inhibitor halofuginone, a derivative of a compound used to treat malaria, indicates that (through interactions with ATP) halofuginone occupies both the amino acid and tRNA binding sites on the synthetase, revealing a new model for developing synthetase inhibitors.

Huihao Zhou
Litao Sun
Paul Schimmel
Research23 Dec 2012
Nature

Volume: 494, P: 121-124
New functions of aminoacyl-tRNA synthetases beyond translation

Aminoacyl tRNA synthetases (aaRSs) have progressively added domains and motifs that have no connection to aminoacylation. These additions equip aaRSs with new functions and correlate with the appearance of new biological processes (such as a circulatory system) during the course of evolution.

Min Guo
Xiang-Lei Yang
Paul Schimmel
Reviews11 Aug 2010
Nature Reviews Molecular Cell Biology

Volume: 11, P: 668-674
Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase

Reveromycin A (RM-A) selectively inhibits eukaryotic cytoplasmic isoleucyltRNA synthetase (IleRS). Herein, the authors show that RM-A molecule occupies the tRNA^Ile binding site of Saccharomyces cerevisiae IleRS, and that RM-A cooperates with isoleucine or isoleucyl-adenylate for IleRS binding.

Bingyi Chen
Siting Luo
Huihao Zhou
ResearchOpen Access12 Mar 2021
Nature Communications

Volume: 12, P: 1-10
Tyrosyl-tRNA synthetase has a noncanonical function in actin bundling

Mutations in tRNA ligases, essential components of the translational machinery, are associated with Charcot-Marie-Tooth peripheral neuropathy, but the mechanistic details are not known. The authors report that the tyrosyl-tRNA synthetase is an evolutionary-conserved F-actin organizer, and dysregulation of this function is associated with the disorder.

Biljana Ermanoska
Bob Asselbergh
Albena Jordanova
ResearchOpen Access08 Mar 2023
Nature Communications

Volume: 14, P: 1-19
Neuropilin 1 and its inhibitory ligand mini-tryptophanyl-tRNA synthetase inversely regulate VE-cadherin turnover and vascular permeability

Functional vascular tree formation is a key step in many contexts, such as cancer, and Neuropilin1 (NRP1) has been associated with adhesion receptor endocytic turnover. Here, authors show NRP1 and its mini-WARS ligand play a role in reducing endothelial permeability.

Noemi Gioelli
Lisa J. Neilson
Guido Serini
ResearchOpen Access20 Jul 2022
Nature Communications

Volume: 13, P: 1-16
Unique ___domain appended to vertebrate tRNA synthetase is essential for vascular development

Seryl-tRNA synthetase is important in vasculogenesis and contains a unique ___domain at its C-terminus. In this study, the unique ___domain is shown to target the protein to the nucleus, block expression ofvegfaand be essential for vasculogenesis in zebrafish.

Xiaoling Xu
Yi Shi
Xiang-Lei Yang
ResearchOpen Access21 Feb 2012
Nature Communications

Volume: 3, P: 1-9
Author Correction: PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications

Junchao Shi
Yunfang Zhang
Qi Chen
Amendments and Corrections29 Apr 2021
Nature Cell Biology

Volume: 23, P: 676
The selective tRNA aminoacylation mechanism based on a single G•U pair

X-ray crystal structures of a tRNA synthetase bound to wild-type and mutant alanine tRNAs reveal the structural basis for selectivity.

Masahiro Naganuma
Shun-ichi Sekine
Shigeyuki Yokoyama
Research11 Jun 2014
Nature

Volume: 510, P: 507-511
Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ and p53 signaling

Trp-tRNA synthetase (TrpRS) has a well-understood role in translation by facilitating aminoacylation of Trp-tRNAs. The discovery of a nuclear signaling role for TrpRS as a bridging protein for DNA-PK and PARP-1, resulting in p53 activation, explains a previously curious link between interferon-γ signaling and concomitant TrpRS overexpression.

Mathew Sajish
Quansheng Zhou
Paul Schimmel
Research15 Apr 2012
Nature Chemical Biology

Volume: 8, P: 547-554
Impaired protein translation in Drosophila models for Charcot–Marie–Tooth neuropathy caused by mutant tRNA synthetases

Charcot–Marie–Tooth (CMT) neuropathy is associated with dominant mutations in five tRNA synthetase genes. Niehues et al. use BONCAT and FUNCAT to monitor proteome dynamics in a DrosophilaCMT model, and reveal that these mutations result in translational slowdown.

Sven Niehues
Julia Bussmann
Erik Storkebaum
ResearchOpen Access03 Jul 2015
Nature Communications

Volume: 6, P: 1-13
Aberrant GlyRS-HDAC6 interaction linked to axonal transport deficits in Charcot-Marie-Tooth neuropathy

Mutations in glycyl-tRNA synthetase (GlyRS) cause Charcot-Marie-Tooth disease, a neuromuscular disorder characterized by axonal degeneration. Here the authors show that mutant GlyRS interacts with histone deacetylase 6, resulting in increased deacetylation of α-tubulin and axonal transport deficits.

Zhongying Mo
Xiaobei Zhao
Xiang-Lei Yang
ResearchOpen Access08 Mar 2018
Nature Communications

Volume: 9, P: 1-11
Neddylation requires glycyl-tRNA synthetase to protect activated E2

Biochemical, structural and cell-based analyses reveal a chaperone-like function of glycyl-tRNA synthetase, which supports neddylation via direct interactions with NEDD8, E1 and E2.

Zhongying Mo
Qian Zhang
Xiang-Lei Yang
Research27 Jun 2016
Nature Structural & Molecular Biology

Volume: 23, P: 730-737
Two classes give lessons about CCA

In a world where nature has designed elegant template-dependent mechanisms for the reproduction of nucleic acid sequences, template-independent RNA polymerases have long been mysterious. Now, two papers provide structural insight into one of these template-independent systems—the addition of the sequence CCA onto the 3′ ends of transfer RNAs.

Paul Schimmel
Xiang-Lei Yang
News & Views01 Sept 2004
Nature Structural & Molecular Biology

Volume: 11, P: 807-808
PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications

Shi et al. profiled small non-coding RNAs (sncRNAs) through PANDORA-seq, which identified tissue-specific transfer RNA- and ribosomal RNA-derived small RNAs, as well as sncRNAs, with dynamic changes during induced pluripotent stem cell reprogramming.

Junchao Shi
Yunfang Zhang
Qi Chen
Research05 Apr 2021
Nature Cell Biology

Volume: 23, P: 424-436
Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma

Alanyl-tRNA synthetases (AlaRSs) may confuse glycine or serine with alanine, potentially causing mistranslation and thus profound functional consequences, with serine posing a bigger challenge than glycine. AlaXps — free-standing, genome-encoded editing proteins — represent one editing checkpoint to prevent this from occurring. Nine crystal structures, together with kinetic and mutational analysis, now show how AlaXps solve the serine misactivation problem.

Min Guo
Yeeting E. Chong
Paul Schimmel
Research10 Dec 2009
Nature

Volume: 462, P: 808-812
CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase

Charcot–Marie–Tooth diseases are hereditary peripheral neuropathies for which there are currently no effective therapies; here the type 2D subtype of these diseases is shown to be caused by mutations impeding a signalling pathway necessary for motor neuron survival.

Weiwei He
Ge Bai
Xiang-Lei Yang
Research21 Oct 2015
Nature

Volume: 526, P: 710-714
Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein

Lin Wang
Yan Wu
Fang Bai
Research04 Aug 2021
Acta Pharmacologica Sinica

Volume: 43, P: 788-796
Glucose-sensitive acetylation of Seryl tRNA synthetase regulates lipid synthesis in breast cancer

Jin Zhao
Hangming Bai
Yi Shi
ResearchOpen Access16 Aug 2021
Signal Transduction and Targeted Therapy

Volume: 6, P: 1-12
Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses

Ryan A. Adams
Cátia Fernandes-Cerqueira
Paul Schimmel
ResearchOpen Access04 Dec 2019
Cellular & Molecular Immunology

Volume: 18, P: 1463-1475
Neuropilin 1 sequestration by neuropathogenic mutant glycyl-tRNA synthetase is permissive to vascular homeostasis

James N. Sleigh
Adriana Gómez-Martín
Giampietro Schiavo
ResearchOpen Access23 Aug 2017
Scientific Reports

Volume: 7, P: 1-11

Search

Organocatalytic asymmetric α-C–H functionalization of alkyl amines

Orthogonal use of a human tRNA synthetase active site to achieve multifunctionality

Correction: Corrigendum: Impaired protein translation in Drosophila models for Charcot–Marie–Tooth neuropathy caused by mutant tRNA synthetases

Correction: Corrigendum: CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase

Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy

Author Correction: Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase

Author Correction: The selective tRNA aminoacylation mechanism based on a single G•U pair

ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase

New functions of aminoacyl-tRNA synthetases beyond translation

Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase

Tyrosyl-tRNA synthetase has a noncanonical function in actin bundling

Neuropilin 1 and its inhibitory ligand mini-tryptophanyl-tRNA synthetase inversely regulate VE-cadherin turnover and vascular permeability

Unique ___domain appended to vertebrate tRNA synthetase is essential for vascular development

Author Correction: PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications

The selective tRNA aminoacylation mechanism based on a single G•U pair

Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ and p53 signaling

Impaired protein translation in Drosophila models for Charcot–Marie–Tooth neuropathy caused by mutant tRNA synthetases

Aberrant GlyRS-HDAC6 interaction linked to axonal transport deficits in Charcot-Marie-Tooth neuropathy

Neddylation requires glycyl-tRNA synthetase to protect activated E2

Two classes give lessons about CCA

PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications

Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma

CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase

Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein

Glucose-sensitive acetylation of Seryl tRNA synthetase regulates lipid synthesis in breast cancer

Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses

Neuropilin 1 sequestration by neuropathogenic mutant glycyl-tRNA synthetase is permissive to vascular homeostasis

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