Elaborate uORF/IRES features control expression and localization of human glycyl-tRNA synthetase

RNA Biology
Jana AlexandrovaMagali Frugier

Abstract

The canonical activity of glycyl-tRNA synthetase (GARS) is to charge glycine onto its cognate tRNAs. However, outside translation, GARS also participates in many other functions. A single gene encodes both the cytosolic and mitochondrial forms of GARS but 2 mRNA isoforms were identified. Using immunolocalization assays, in vitro translation assays and bicistronic constructs we provide experimental evidence that one of these mRNAs tightly controls expression and localization of human GARS. An intricate regulatory domain was found in its 5'-UTR which displays a functional Internal Ribosome Entry Site and an upstream Open Reading Frame. Together, these elements hinder the synthesis of the mitochondrial GARS and target the translation of the cytosolic enzyme to ER-bound ribosomes. This finding reveals a complex picture of GARS translation and localization in mammals. In this context, we discuss how human GARS expression could influence its moonlighting activities and its involvement in diseases.

References

May 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·M Kozak
Apr 25, 1995·Nucleic Acids Research·J WilliamsD Power
Mar 7, 2000·Oncogene·M J ColdwellA E Willis
Aug 10, 2000·The Journal of Biological Chemistry·R M Seiser, C V Nicchitta
Aug 31, 2000·Journal of Molecular Biology·C NotredameJ Heringa
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·J K PinkstaffL A Krushel
Apr 12, 2003·American Journal of Human Genetics·Anthony AntonellisEric D Green
Jan 12, 2005·Briefings in Functional Genomics & Proteomics·Hervé ChabanonJohn Hesketh
Jan 25, 2005·Chemistry & Biology·Aurélie Lescoute, Eric Westhof
Jun 1, 2005·Biochimie·Michaël RyckelynckMagali Frugier
Oct 13, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Anthony AntonellisEric D Green
Jun 27, 2007·Nucleic Acids Research·Stephen D BairdMartin Holcik
Jun 5, 2008·FEMS Microbiology Reviews·Corinne D Hausmann, Michael Ibba
Aug 14, 2008·RNA·Václav VopálenskýMartin Pospísek
Apr 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sarah E CalvoVamsi K Mootha
Jan 23, 2010·Nature Reviews. Molecular Cell Biology·Richard J JacksonTatyana V Pestova
Feb 16, 2010·Trends in Neurosciences·William W MotleyKenneth H Fischbeck
Oct 23, 2010·Molecular Cell·Keith A SpriggsAnne E Willis
Jan 12, 2011·Cell Cycle·Anton A Komar, Maria Hatzoglou
Apr 5, 2011·The Journal of Biological Chemistry·Alexandre DavidJonathan W Yewdell
Sep 3, 2011·Microbiology and Molecular Biology Reviews : MMBR·Alan G Hinnebusch
Sep 24, 2011·Nature Reviews. Cancer·Sunghoon KimDaehee Hwang
Jan 17, 2012·Advances in Protein Chemistry and Structural Biology·Richard J JacksonTatyana V Pestova
Feb 22, 2012·Proceedings of the National Academy of Sciences of the United States of America·Min Chul ParkSunghoon Kim
Mar 1, 2012·Nucleic Acids Research·Dmitri E AndreevIvan N Shatsky
Jan 3, 2013·Journal of the Peripheral Nervous System : JPNS·Hye Jin LeeKi Wha Chung
Jan 29, 2013·Biochimica Et Biophysica Acta·Orit Hermesh, Ralf-Peter Jansen
Feb 19, 2013·Nature Chemical Biology·Min Guo, Paul Schimmel
Feb 22, 2013·EMBO Molecular Medicine·Peng Yao, Paul L Fox
Mar 5, 2013·Biochimica Et Biophysica Acta·Benjamin L WeisWilliam Zerges
Mar 8, 2013·Current Opinion in Genetics & Development·Rachel C Wallen, Anthony Antonellis
Jan 16, 2014·Autoimmunity Reviews·Michael MahlerMarvin J Fritzler

❮ Previous
Next ❯

Citations

Oct 26, 2016·Methods : a Companion to Methods in Enzymology·Sylvain DebardHubert Dominique Becker
Nov 15, 2016·RNA Biology·Serena BernacchiJean-Christophe Paillart
Sep 2, 2020·Wiley Interdisciplinary Reviews. RNA·Christina Akirtava, Charles Joel McManus
Mar 10, 2018·Frontiers in Molecular Neuroscience·Stuart J GriceM Zameel Cader
Jul 25, 2020·Cell Death & Disease·James N SleighGiampietro Schiavo
Jan 22, 2019·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·P CorciaP Vourc'h
Jun 12, 2019·IUBMB Life·Catherine Florentz, Richard Giegé
Aug 28, 2020·Frontiers in Cellular Neuroscience·James N SleighGiampietro Schiavo

❮ Previous
Next ❯

Methods Mentioned

BETA
aminoacylation
PCR
PCRs
transfection
protein assay

Software Mentioned

Tcoffee
Assemble
LocARNA

Related Concepts

Related Feeds

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.