Functional interaction between FUS and SMN underlies SMA-like splicing changes in wild-type hFUS mice

Scientific Reports
Alessia MirraMauro Cozzolino

Abstract

Several of the identified genetic factors in Amyotrophic Lateral Sclerosis (ALS) point to dysfunction in RNA processing as a major pathogenic mechanism. However, whether a precise RNA pathway is particularly affected remains unknown. Evidence suggests that FUS, that is mutated in familial ALS, and SMN, the causative factor in Spinal Muscular Atrophy (SMA), cooperate to the same molecular pathway, i.e. regulation of alternative splicing, and that disturbances in SMN-regulated functions, either caused by depletion of SMN protein (as in the case of SMA) or by pathogenic interactions between FUS and SMN (as in the case of ALS) might be a common theme in both diseases. In this work, we followed these leads and tested their pathogenic relevance in vivo. FUS-associated ALS recapitulates, in transgenic mice, crucial molecular features that characterise mouse models of SMA, including defects in snRNPs distribution and in the alternative splicing of genes important for motor neurons. Notably, altering SMN levels by haploinsufficiency or overexpression does not impact the phenotypes of mouse or Drosophila models of FUS-mediated toxicity. Overall, these findings suggest that FUS and SMN functionally interact and that FUS may act downstream...Continue Reading

References

Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·B SchrankM Sendtner
Sep 16, 2008·PloS One·Howard Chia-Hao ChangSpyros Artavanis-Tsakonas
Aug 11, 2011·Human Molecular Genetics·Maria Grazia PesaresiMauro Cozzolino
Nov 1, 2011·Molecular and Cellular Biology·Matteo RuggiuLivio Pellizzoni
Jan 10, 2012·Neurobiology of Disease·Takuto HideyamaShin Kwak
Oct 2, 2012·Cell Reports·Tomohiro YamazakiRobin Reed
Oct 16, 2012·Cell·Francesco LottiLivio Pellizzoni
Mar 26, 2013·Neurobiology of Disease·Valeria GerbinoTilmann Achsel
May 18, 2013·Human Molecular Genetics·Ewout J N GroenR Jeroen Pasterkamp
Nov 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Zhenxi ZhangGideon Dreyfuss
Nov 22, 2013·Biochemical Society Transactions·Tilmann AchselMaria Teresa Carrì
Oct 23, 2015·Cell Death & Disease·M Di SalvioG Cestra
Jan 19, 2016·Brain Pathology·Simona RossiMaria Teresa Carrì
Jun 3, 2016·The EMBO Journal·Stefan ReberMarc-David Ruepp
Jun 28, 2016·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Hitoshi AizawaShin Kwak
Aug 9, 2016·Brain : a Journal of Neurology·Sonja Prpar MihevcBoris Rogelj
Sep 8, 2016·Acta Neuropathologica Communications·Matthew NolanOlaf Ansorge

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Citations

Dec 23, 2017·Frontiers in Molecular Neuroscience·Andrew P Tosolini, James N Sleigh
Jun 4, 2019·Frontiers in Molecular Neuroscience·Ashlyn M SpringA Gregory Matera
Aug 22, 2018·Journal of Developmental Biology·Eugenia C Olesnicky, Ethan G Wright
Mar 2, 2021·Neural Regeneration Research·Jin-Xin LuGang Chen
Nov 7, 2020·International Journal of Molecular Sciences·Jonathan Fernando Reinoso-SánchezManuela Cervelli
Jul 25, 2021·International Journal of Molecular Sciences·Eleonora StronatiEmanuele Cacci
Nov 18, 2021·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration

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Methods Mentioned

BETA
SMA
transgenic
deamination
PCR
immunoprecipitation
protein assay

Software Mentioned

Adobe Photoshop
Lightcycler
ImageJ
MedCalc

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