U1 snRNP is mislocalized in ALS patient fibroblasts bearing NLS mutations in FUS and is required for motor neuron outgrowth in zebrafish

Nucleic Acids Research
Yong YuRobin Reed

Abstract

Mutations in FUS cause amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to neurodegeneration remain obscure. We previously found that U1 snRNP is the most abundant FUS interactor. Here, we report that components of the U1 snRNP core particle (Sm proteins and U1 snRNA), but not the mature U1 snRNP-specific proteins (U1-70K, U1A and U1C), co-mislocalize with FUS to the cytoplasm in ALS patient fibroblasts harboring mutations in the FUS nuclear localization signal (NLS). Similar results were obtained in HeLa cells expressing the ALS-causing FUS R495X NLS mutation, and mislocalization of Sm proteins is RRM-dependent. Moreover, as observed with FUS, knockdown of any of the U1 snRNP-specific proteins results in a dramatic loss of SMN-containing Gems. Significantly, knockdown of U1 snRNP in zebrafish results in motor axon truncations, a phenotype also observed with FUS, SMN and TDP-43 knockdowns. Our observations linking U1 snRNP to ALS patient cells with FUS mutations, SMN-containing Gems, and motor neurons indicate that U1 snRNP is a component of a molecular pathway associated with motor neuron disease. Linking an essential canonical splicing factor (U1 snRNP) to this pathway provides strong new evidence that ...Continue Reading

References

Dec 3, 2002·Science·Livio PellizzoniGideon Dreyfuss
Mar 27, 2007·Cold Spring Harbor Symposia on Quantitative Biology·D J BattleG Dreyfuss
Mar 1, 2008·Science·Jemeen SreedharanChristopher E Shaw
Sep 20, 2008·PLoS Genetics·Nicola J RutherfordRosa Rademakers
Mar 17, 2010·Trends in Neurosciences·Robin LemmensWim Robberecht
Jun 2, 2010·Molecular Cell·Jeongsik YongGideon Dreyfuss
Jul 28, 2010·Neurology·S WaibelA C Ludolph
Aug 12, 2010·Human Molecular Genetics·Daryl A BoscoLawrence J Hayward
Aug 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Xiu ShanPhilip C Wong
Sep 2, 2010·PloS One·Aaron VoigtJörg B Schulz
Oct 1, 2010·Nature·Daisuke KaidaGideon Dreyfuss
Aug 19, 2011·Prion·Aaron D Gitler, James Shorter
Nov 15, 2011·Nature Structural & Molecular Biology·Jessica I HoellThomas Tuschl
Dec 1, 2011·Nature Reviews. Neuroscience·Edward B LeeJohn Q Trojanowski
Mar 13, 2012·Brain Research·Colleen M DeweyGang Yu
Oct 2, 2012·Cell Reports·Tomohiro YamazakiRobin Reed
Dec 12, 2012·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·S WaibelA C Ludolph
Dec 21, 2012·EMBO Molecular Medicine·Hitomi TsuijiKoji Yamanaka
Mar 7, 2013·Nature Reviews. Neuroscience·Wim Robberecht, Thomas Philips
Mar 26, 2013·Neurobiology of Disease·Valeria GerbinoTilmann Achsel
May 1, 2013·The Journal of Cell Biology·Yun R LiAaron D Gitler
May 18, 2013·Human Molecular Genetics·Ewout J N GroenR Jeroen Pasterkamp
Jul 9, 2013·Cell Reports·Takashi NonakaMasato Hasegawa
Aug 13, 2013·Neuron·Shuo-Chien LingDon W Cleveland
Aug 21, 2013·Cell·Mani RamaswamiRoy Parker
Nov 26, 2013·Cell Reports·Jacob C SchwartzThomas R Cech
Dec 27, 2013·Nature Neuroscience·Alan E RentonBryan J Traynor
Feb 11, 2014·The Journal of Clinical Investigation·Haiyan QiuEric J Huang
Apr 2, 2014·Nature Neuroscience·Janel O JohnsonBryan J Traynor
May 2, 2014·Experimental Neurology·Claire S LeblondGuy A Rouleau

❮ Previous
Next ❯

Citations

Nov 4, 2015·Biomolecules·Lulzim Shkreta, Benoit Chabot
Jan 30, 2016·Wiley Interdisciplinary Reviews. RNA·Akio MasudaKinji Ohno
Jul 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Yong Yu, Robin Reed
Jan 6, 2016·The Journal of Cell Biology·Benoit Chabot, Lulzim Shkreta
Dec 23, 2015·Trends in Molecular Medicine·Diana Caballero-HernandezDavid Pozo
Jan 19, 2016·Brain Pathology·Simona RossiMaria Teresa Carrì
Jun 7, 2016·Neuropharmacology·Jong-Min LeeGilles J Guillemin
Jun 16, 2016·RNA Biology·Šárka Růžičková, David Staněk
Mar 5, 2016·Journal of Neurochemistry·Hilary A Bowden, Dorothee Dormann
Mar 27, 2016·Journal of Neurochemistry·Antonia Ratti, Emanuele Buratti
Sep 16, 2016·RNA Biology·David Staněk
Feb 1, 2018·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Philippe CodronArnaud Chevrollier
Jun 23, 2018·Traffic·Thomas W KirbyRobert E London
Sep 7, 2017·RNA Biology·Pilar Vazquez-Arango, Dawn O'Reilly
Jun 3, 2016·The EMBO Journal·Stefan ReberMarc-David Ruepp
Dec 23, 2017·Frontiers in Molecular Neuroscience·Andrew P Tosolini, James N Sleigh
Mar 20, 2020·International Journal of Molecular Sciences·Ken-Ichi FujitaSeiji Masuda
Apr 24, 2017·Human Genetics·Vittoria PagliariniClaudio Sette
Aug 29, 2020·Journal of Personalized Medicine·Laura Le GallStephanie Duguez
Aug 1, 2020·Frontiers in Neuroscience·Ramya RanganathanJanine Kirby
Jun 24, 2017·Frontiers in Molecular Biosciences·Maia LanfrancoRuben J Cauchi
Feb 7, 2019·Frontiers in Genetics·Zoe Butti, Shunmoogum A Patten
Aug 3, 2019·Cold Spring Harbor Perspectives in Biology·Karla M Neugebauer
Mar 22, 2019·Wiley Interdisciplinary Reviews. RNA·Sara Nik, Teresa V Bowman
Mar 2, 2021·Neural Regeneration Research·Katherine L Marshall, Mohamed H Farah
May 4, 2021·Journal of Proteome Research·Lucas VuChristine Vande Velde
Sep 28, 2021·Frontiers in Molecular Biosciences·Kai-Lu ZhangShao-Ming Zhou
Aug 8, 2015·Genes & Development·Tristan H Coady, James L Manley

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
transgenic
co-IP

Software Mentioned

Metamorph
LSM
SDS
- Sharp
GraphPad
Prism
Laser

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.

Cajal Bodies & Gems

Cajal bodies or coiled bodies are dense foci of coilin protein. Gemini of Cajal bodies, or gems, are microscopically similar to Cajal bodies. It is believed that Cajal bodies play important roles in RNA processing while gems assist the Cajal bodies. Find the latest research on Cajal bodies and gems here.

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: Phenotypes

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized phenotypically by progressive muscle weakness. Clinical phenotypes of ALS can be classified based on the pattern, level, and area of onset (e.g. bulbar, cervical, lumbar). Here is the latest research investigating phenotypes of ALS.

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.