Amino-acid-dependent shift in tRNA synthetase editing mechanisms

Journal of the American Chemical Society
Jaya Sarkar, Susan A Martinis

Abstract

Many aminoacyl-tRNA synthetases prevent mistranslation by relying upon proofreading activities at multiple stages of the aminoacylation reaction. In leucyl-tRNA synthetase (LeuRS), editing activities that precede or are subsequent to tRNA charging have been identified. Although both are operational, either the pre- or post-transfer editing activity can predominate. Yeast cytoplasmic LeuRS (ycLeuRS) misactivates structurally similar noncognate amino acids including isoleucine and methionine. We show that ycLeuRS has a robust post-transfer editing activity that efficiently clears tRNA(Leu) mischarged with isoleucine. In comparison, the enzyme's post-transfer hydrolytic activity against tRNA(Leu) mischarged with methionine is weak. Rather, methionyl-adenylate is cleared robustly via an enzyme-mediated pre-transfer editing activity. We hypothesize that, similar to E. coli LeuRS, ycLeuRS has coexisting functional pre- and post-transfer editing activities. In the case of ycLeuRS, a shift between the two editing pathways is triggered by the identity of the noncognate amino acid.

References

Feb 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Li LiMichal T Boniecki
Jul 10, 2012·The Journal of Biological Chemistry·Jiqiang LingMiljan Simonovic
Apr 8, 2014·Wiley Interdisciplinary Reviews. RNA·Yan Ling Joy PangSusan A Martinis
Aug 25, 2017·Nature Microbiology·Kyle Mohler, Michael Ibba
Jun 27, 2015·Nature Communications·Sadeem AhmadRajan Sankaranarayanan
Jul 15, 2018·Nucleic Acids Research·Stephanie M ZimmermanEric M Phizicky

Citations

Jan 1, 1995·Trends in Biochemical Sciences·P Schimmel, E Schmidt
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·H Y KimH Jakubowski
Aug 31, 2000·Annual Review of Biochemistry·Michael Ibba, Dieter Söll
Jun 20, 2002·Journal of the American Chemical Society·Richard S Mursinna, Susan A Martinis
Apr 30, 2003·Molecular Cell·Tommie L LincecumStephen Cusack
Apr 23, 2005·The Journal of Biological Chemistry·Ita Gruic-SovuljJohn J Perona
May 12, 2005·The Journal of Biological Chemistry·Benfang Ruan, Dieter Söll
Aug 10, 2005·The Journal of Biological Chemistry·Songon An, Karin Musier-Forsyth
Mar 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Amy M Williams, Susan A Martinis
Sep 25, 2007·Journal of Bacteriology·Vrajesh A KarkhanisSusan A Martinis
Jan 9, 2008·The Journal of Biological Chemistry·Kathryn E SplanKarin Musier-Forsyth
Nov 21, 2008·Proceedings of the National Academy of Sciences of the United States of America·Michal T BonieckiSusan A Martinis
Dec 11, 2008·The Journal of Biological Chemistry·Bin ZhuEn-Duo Wang
Apr 22, 2009·Annual Review of Microbiology·Jiqiang LingMichael Ibba
May 26, 2010·The Journal of Biological Chemistry·Morana DulicIta Gruic-Sovulj
May 28, 2010·The Journal of Biological Chemistry·Anand Minajigi, Christopher S Francklyn
May 25, 2011·Proceedings of the National Academy of Sciences of the United States of America·Li LiSusan A Martinis

Related Concepts

LARS gene
Alkalescens-Dispar Group
Amino Acids, I.V. solution additive
Yeasts
Transfer RNA
Amino Acyl-tRNA Synthetases
Leucine-Specific tRNA
Isoleucine
LARS2 gene
Methionine

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Synapse Loss as Therapeutic Target in MS

As we age, the number of synapses present in the human brain starts to decline, but in neurodegenerative diseases this occurs at an accelerated rate. In MS, it has been shown that there is a reduction in synaptic density, which presents a potential target for treatment. Here is the latest research on synapse loss as a therapeutic target in MS.

Artificial Intelligence in Cardiac Imaging

Artificial intelligence (ai) techniques are increasingly applied to cardiovascular (cv) medicine in cardiac imaging analysis. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

Social Learning

Social learning involves learning new behaviors through observation, imitation and modeling. Follow this feed to stay up to date on the latest research.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Single Cell Chromatin Profiling

Techniques like ATAC-seq and CUT&Tag have the potential to allow single cell profiling of chromatin accessibility, histones, and TFs. This will provide novel insight into cellular heterogeneity and cell states. Discover the latest research on single cell chromatin profiling here.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.