Proteomic analyses reveal that loss of TDP-43 affects RNA processing and intracellular transport

Neuroscience
M ŠtalekarBoris Rogelj

Abstract

Transactive response DNA-binding protein 43 (TDP-43) is a predominantly nuclear, ubiquitously expressed RNA and DNA-binding protein. It recognizes and binds to UG repeats and is involved in pre-mRNA splicing, mRNA stability and microRNA metabolism. TDP-43 is essential in early embryonic development but accumulates in cytoplasmic aggregates in amyotrophic lateral sclerosis (ALS) and tau-negative frontotemporal lobar degeneration (FTLD). It is not known yet whether cytoplasmic aggregates of TDP-43 are toxic or protective but they are often associated with a loss of TDP-43 from the nucleus and neurodegeneration may be caused by a loss of normal TDP-43 function or a gain of toxic function. Here we present a proteomic study to analyze the effect of loss of TDP-43 on the proteome. MS data are available via ProteomeXchange with identifier PXD001668. Our results indicate that TDP-43 is an important regulator of RNA metabolism and intracellular transport. We show that Ran-binding protein 1 (RanBP1), DNA methyltransferase 3 alpha (Dnmt3a) and chromogranin B (CgB) are downregulated upon TDP-43 knockdown. Subsequently, transportin 1 level is increased as a result of RanBP1 depletion. Improper regulation of these proteins and the subsequent...Continue Reading

References

Mar 29, 1994·Proceedings of the National Academy of Sciences of the United States of America·F R BischoffH Ponstingl
Jul 28, 1999·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·M LandénK Blennow
Nov 25, 2003·Analytical Chemistry·Alexey I NesvizhskiiRuedi Aebersold
Sep 13, 2005·Experimental Neurology·Ulla RüetschiKaj Blennow
May 30, 2006·Developmental Biology·Kshitish K AcharyaPrabhakara P Reddi
Feb 22, 2008·Annals of Neurology·Michael A GitchoNigel J Cairns
Feb 29, 2008·Proceedings of the National Academy of Sciences of the United States of America·Youhna M AyalaFrancisco E Baralle
Mar 1, 2008·Science·Jemeen SreedharanChristopher E Shaw
Apr 29, 2008·Annals of Neurology·Akio YokosekiOsamu Onodera
Aug 30, 2008·Regulatory Peptides·A Schrott-FischerJ Marksteiner
Sep 20, 2008·PLoS Genetics·Nicola J RutherfordRosa Rademakers
Sep 22, 2009·Journal of Neurochemistry·Claudia ColombritaAntonia Ratti
Oct 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Iga WegorzewskaRobert H Baloh
Dec 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Francois Gros-LouisJean-Pierre Julien
Mar 4, 2010·Acta Neuropathologica·Brian C KraemerGerard D Schellenberg
Apr 29, 2010·The FEBS Journal·Emanuele BurattiFrancisco Baralle
Jul 8, 2010·The EMBO Journal·Dorothee DormannChristian Haass
Mar 2, 2011·Nature Neuroscience·James R TollerveyJernej Ule
Mar 2, 2011·Nature Neuroscience·Magdalini PolymenidouDon W Cleveland
Aug 4, 2011·Journal of Molecular Neuroscience : MN·Tania F Gendron, Leonard Petrucelli
Aug 19, 2011·Acta Neuropathologica·Jack BrelstaffTamas Revesz
Nov 5, 2011·The Journal of Biological Chemistry·Jayarama Krishnan BoseC-K James Shen
Nov 18, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Barry A ChestnutLee J Martin
May 23, 2012·Brain Research·William TsaoPhilip C Wong
Feb 1, 2013·Neuropathology and Applied Neurobiology·R TakeuchiH Takahashi

❮ Previous
Next ❯

Citations

Dec 23, 2015·Trends in Molecular Medicine·Diana Caballero-HernandezDavid Pozo
Nov 1, 2015·Biochimica Et Biophysica Acta·Claudia ColombritaAntonia Ratti
Jun 9, 2016·Acta Neuropathologica·Steven BoeynaemsLudo Van Den Bosch
Dec 5, 2015·Journal of Applied Genetics·Anna Y Tang
Aug 9, 2016·Brain : a Journal of Neurology·Sonja Prpar MihevcBoris Rogelj
Mar 27, 2016·Journal of Neurochemistry·Antonia Ratti, Emanuele Buratti
Jan 4, 2017·Scientific Reports·Takenari YamashitaShin Kwak
Apr 6, 2017·FEBS Letters·Helena Ederle, Dorothee Dormann
Oct 29, 2018·Acta Neuropathologica·Sarat C VatsavayaiWilliam W Seeley
Feb 12, 2019·Critical Reviews in Biochemistry and Molecular Biology·S ParakhJ D Atkin
May 28, 2017·BMC Medical Genomics·Jack HumphreyVincent Plagnol
Jun 28, 2019·Frontiers in Neuroscience·Thomas J HedlAlbert Lee
Sep 19, 2019·Life Science Alliance·Agnes Roczniak-Ferguson, Shawn M Ferguson
Dec 5, 2018·Acta Neuropathologica·Alissa L NanaWilliam W Seeley
Nov 14, 2019·Neural Regeneration Research·Fausta CiccocioppoSebastiano Miscia
May 21, 2021·Molecular and Cellular Neurosciences·Rachel A K AtkinsonAnna E King
Nov 12, 2021·Expert Review of Proteomics·Alexander G ThompsonMartin R Turner

❮ Previous
Next ❯

Related Concepts

Related Feeds

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

ALS: Stress Granules

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by cytoplasmic protein aggregates within motor neurons. TDP-43 is an ALS-linked protein that is known to regulate splicing and storage of specific mRNAs into stress granules, which have been implicated in formation of ALS protein aggregates. Here is the latest research in this field.

ALS & FTD: TDP-43

TAR DNA-binding protein 43 (TDP-43) is a pathological protein identified in sporadic Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Here are the latest discoveries pertaining to TDP-43 and these diseases.

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.

ALS: Pathogenic Mechanisms

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating pathogenic mechanisms that underlie this genetically heterogeneous disorder.

Related Papers

The International Journal of Biochemistry & Cell Biology
Sadaf T WarraichIan P Blair
Acta Neuropathologica Communications
Rui LiuMax S Cynader
Human Molecular Genetics
Clotilde Lagier-TourenneDon W Cleveland
© 2022 Meta ULC. All rights reserved