Wild-type and mutant SOD1 localizes to RNA-rich structures in cells and mice but does not bind RNA.

Journal of Neurochemistry
Matteo Da RosDerrick Gibbings

Abstract

Many of the genes whose mutation causes Amyotrophic Lateral Sclerosis (ALS) are RNA-binding proteins which localize to stress granules, while others impact the assembly, stability, and elimination of stress granules. This has led to the hypothesis that alterations in the dynamics of stress granules and RNA biology cause ALS. Genetic mutations in Superoxide Dismutase 1 (SOD1) also cause ALS. Evidence demonstrates that SOD1 harboring ALS-linked mutations is recruited to stress granules, induces changes in alternative splicing, and could be an RNA-binding protein. Whether SOD1 inclusions contain RNA in disease models and whether SOD1 directly binds RNA remains uncertain. We applied methods including cross-linking immunoprecipitation and in vitro gel shift assays to detect binding of SOD1 to RNA in vitro, in cells with and without stress granules, and in mice expressing human SOD1 G93A. We find that SOD1 localizes to RNA-rich structures including stress granules, and SOD1 inclusions in mice contain mRNA. However, we find no evidence that SOD1 directly binds RNA. This suggests that SOD1 may impact stress granules, alternative splicing and RNA biology without binding directly to RNA.

References

Aug 16, 1994·Proceedings of the National Academy of Sciences of the United States of America·D R BorcheltD W Cleveland
Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·T J LyonsJ S Valentine
May 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·P B StathopulosE M Meiering
Oct 28, 2004·The Journal of Biological Chemistry·Wei-Wen GeMichael J Strong
Mar 31, 2006·Molecular & Cellular Proteomics : MCP·Thomas J LukasTeepu Siddique
Dec 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Mikiei TanakaEarl R Stadtman
Jan 20, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Julie Deschênes-FurryBernard J Jasmin
Jul 27, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Liang LuPeter H King
Aug 24, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Laura FerraiuoloPamela J Shaw
Mar 10, 2009·The Journal of Biological Chemistry·Jungmook LyuWange Lu
Jun 19, 2009·Nature·Sung Wook ChiRobert B Darnell
Jan 25, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kenrick A VassallElizabeth M Meiering
Jan 10, 2013·PloS One·Urmi BandyopadhyayArthur L Horwich
May 1, 2013·The Journal of Cell Biology·Yun R LiAaron D Gitler
Aug 6, 2013·Nature Structural & Molecular Biology·S Chul KwonV Narry Kim
Mar 29, 2014·Nature·Steve Perrin
Feb 6, 2015·Frontiers in Cellular Neuroscience·Alexandre HenriquesArmin Schneider
Mar 25, 2015·Nature Neuroscience·Axel FreischmidtJochen H Weishaupt
Dec 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Shuying SunDon W Cleveland
Jan 1, 2016·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth A ProctorNikolay V Dokholyan
Aug 3, 2016·Acta Neuropathologica·Jozsef GalHaining Zhu
Nov 11, 2016·Nature·J Paul TaylorDon W Cleveland
Mar 2, 2017·Acta Neuropathologica·Sandrine Da CruzJohn Ravits
Oct 28, 2017·Nucleic Acids Research·Tala BakheetKhalid S A Khabar
Mar 24, 2018·Neuron·Aude NicolasJohn E Landers
Apr 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·Cheng ZhuNikolay V Dokholyan
May 24, 2018·Nature Communications·Raphaelle LuisierRickie Patani
Jul 20, 2018·Nature Communications·Maneka ChitiproluDerrick Gibbings
Sep 23, 2018·Scientific Reports·Bastien ParéFrançois Gros-Louis
Mar 4, 2019·Neuron·Jacob R MannChristopher J Donnelly

❮ Previous
Next ❯

Citations

Jan 20, 2021·Current Opinion in Structural Biology·Esther S Choi, Nikolay V Dokholyan
Apr 4, 2021·International Journal of Molecular Sciences·Wanil KimKyung-Ha Lee
Nov 18, 2021·Journal of the American Chemical Society·Nirnay SamantaSimon Ebbinghaus

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.

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: 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.

© 2021 Meta ULC. All rights reserved