Elongator and codon bias regulate protein levels in mammalian peripheral neurons.

Nature Communications
Joy GoffenaLynn George

Abstract

Familial dysautonomia (FD) results from mutation in IKBKAP/ELP1, a gene encoding the scaffolding protein for the Elongator complex. This highly conserved complex is required for the translation of codon-biased genes in lower organisms. Here we investigate whether Elongator serves a similar function in mammalian peripheral neurons, the population devastated in FD. Using codon-biased eGFP sensors, and multiplexing of codon usage with transcriptome and proteome analyses of over 6,000 genes, we identify two categories of genes, as well as specific gene identities that depend on Elongator for normal expression. Moreover, we show that multiple genes in the DNA damage repair pathway are codon-biased, and that with Elongator loss, their misregulation is correlated with elevated levels of DNA damage. These findings link Elongator's function in the translation of codon-biased genes with both the developmental and neurodegenerative phenotypes of FD, and also clarify the increased risk of cancer associated with the disease.

References

Jun 1, 1979·Journal of Neurocytology·S N Lawson, T J Biscoe
Aug 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·S YokoyamaT Miyazawa
Jun 17, 1969·Biochimica Et Biophysica Acta·T SekiyaT Ukita
Jan 1, 1995·Progress in Nucleic Acid Research and Molecular Biology·G R Björk
Feb 17, 2001·American Journal of Human Genetics·S A SlaugenhauptJ F Gusella
Mar 10, 2001·Molecular Cell·M E MoynahanM Jasin
Feb 11, 2003·American Journal of Human Genetics·Math P CuajungcoSusan A Slaugenhaupt
Feb 11, 2004·Nature Genetics·Maria-Céu MoreiraMichel Koenig
Feb 24, 2004·Molecular Biology of the Cell·Yaojiong WuBurton B Yang
Feb 26, 2004·Muscle & Nerve·Felicia B Axelrod
Apr 24, 2004·American Journal of Human Genetics·Ying-Zhang ChenPhillip F Chance
Nov 24, 2004·Nature Structural & Molecular Biology·Frank V MurphyPaul F Agris
Jan 7, 2005·Molecular Biology of the Cell·Wang ShengBurton B Yang
Jun 17, 2006·Proceedings of the National Academy of Sciences of the United States of America·Kenji E OriiPeter J McKinnon
May 4, 2007·The EMBO Journal·Pierre-Olivier FrappartPeter J McKinnon
Nov 11, 2008·Human Molecular Genetics·Claire L SimpsonAmmar Al-Chalabi
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Jan 29, 2009·European Journal of Human Genetics : EJHG·Lisa J StrugDeb K Pal
Nov 17, 2009·The Journal of Pediatrics·Gabrielle Gold-von SimsonFelicia B Axelrod
Dec 31, 2010·Amyotrophic Lateral Sclerosis : Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases·Michio HiranoLewis P Rowland
Jul 7, 2012·Cell Reports·Fanelie BauerDamien Hermand
Nov 21, 2012·Cell Cycle·Fanelie Bauer, Damien Hermand
Jul 23, 2013·PLoS Genetics·Jorge Fernández-VázquezElena Hidalgo
Aug 13, 2013·PLoS Genetics·Boris Zinshteyn, Wendy V Gilbert
Sep 17, 2013·Nature Neuroscience·Wen-Yuan WangLi-Huei Tsai
Nov 1, 2013·Proceedings of the National Academy of Sciences of the United States of America·Lynn GeorgeFrances Lefcort
Dec 3, 2014·Biochemical and Biophysical Research Communications·Tony KarlsbornAnders S Byström
Apr 8, 2015·American Journal of Medical Genetics. Part a·Julie S CohenAli Fatemi
May 13, 2015·Bioinformatics·Wencke WalterMercedes Ricote

❮ Previous
Next ❯

Citations

Aug 12, 2018·Nature Communications·Marija KojicBrandon J Wainwright
Jul 17, 2019·Science Advances·Maria I DaudenSebastian Glatt
May 24, 2019·Journal of Virology·Federico ValdezManuel Llano
Sep 15, 2020·Seminars in Neurology·Frances Lefcort
Apr 17, 2020·Nature·Sebastian M WaszakStefan M Pfister
Apr 14, 2020·The Journal of Clinical Investigation·Lin LiWarren G Tourtellotte
Feb 7, 2020·International Journal of Molecular Sciences·Diego Rojas-Benítez, Miguel L Allende
Apr 3, 2020·Current Genetics·Rościsław KrutyhołowaSebastian Glatt
Nov 28, 2018·International Journal of Molecular Sciences·Marisa PereiraAna Raquel Soares
Dec 5, 2020·Trends in Genetics : TIG·Jesus Garcia-LopezPaul A Northcott
Nov 7, 2020·International Journal of Molecular Sciences·Nour-El-Hana AbbassiTing-Yu Lin
Dec 12, 2018·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Jillian Ramos, Dragony Fu
Apr 17, 2021·Nature Communications·Francesca RapinoPierre Close
May 13, 2021·Nature Communications·Marija KojicBrandon J Wainwright
Jan 15, 2021·Annual Review of Biochemistry·Yi LiuFangzhou Zhao
Dec 5, 2018·Biochemistry·Leticia Pollo-Oliveira, Valérie de Crécy-Lagard
Oct 1, 2021·Biology Open·BreAnna CameronLynn George
Dec 14, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Elisabetta MoriniSusan A Slaugenhaupt

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE80130
Mm99999915
PXD007869

Methods Mentioned

BETA
protein folding
ubiquitination
GTPase
electrophoresis
proteomic profiling
Chips
in-vitro transcription
chip
Assay
genotyping

Software Mentioned

QCapture
GOplot R package
ImageJ OpenComet
Arraystar
GOplot
Agilent Qualitative Analysis
Image J
Illumina
Proteome Cluster
DAVID

Related Concepts

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.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

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.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. 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.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society
Frances LefcortLynn George
Current Opinion in Genetics & Development
Susan A Slaugenhaupt, James F Gusella
Proceedings of the National Academy of Sciences of the United States of America
Sarah B OhlenFrances Lefcort
© 2022 Meta ULC. All rights reserved