CoChat
Sign Up
Cited by 92Amyotrophic Lateral Sclerosis ResearchHereditary Neurological DisordersAlzheimer's disease research and treatments

Matrin 3-dependent neurotoxicity is modified by nucleic acid binding and nucleocytoplasmic localization

Open access
Malik, Ahmed M, Miguez, Roberto A, Li, Xingli, Ho, Ye-Shih, Feldman, Eva L, Barmada, Sami J·2018·eLife
DOI 10.7554/elife.35977PMC PMC6050042

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Abnormalities in nucleic acid processing are associated with the development of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mutations in Matrin 3 (MATR3), a poorly understood DNA- and RNA-binding protein, cause familial ALS/FTD, and MATR3 pathology is a feature of sporadic disease, suggesting that MATR3 dysfunction is integrally linked to ALS pathogenesis. Using a rat primary neuron model to assess MATR3-mediated toxicity, we noted that neurons were bidirectionally vulnerable to MATR3 levels, with pathogenic MATR3 mutants displaying enhanced toxicity. MATR3’s zinc finger domains partially modulated toxicity, but elimination of its RNA recognition motifs had no effect on survival, instead facilitating its self-assembly into liquid-like droplets. In contrast to other RNA-binding proteins associated with ALS, cytoplasmic MATR3 redistribution mitigated neurodegeneration, suggesting that nuclear MATR3 mediates toxicity. Our findings offer a foundation for understanding MATR3-related neurodegeneration and how nucleic acid binding functions, localization, and pathogenic mutations drive sporadic and familial disease.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.7554/elife.35977

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Shared genetics underlying both ALS and FTD testify to the close overlap between ALS and FTLD with TDP43 pathology (FTLD-TDP).

    “These observations, as well as shared genetics underlying both ALS and FTD, testify to the close overlap between ALS and FTLD with TDP43 pathology (FTLD-TDP) (3, 45).”

    From Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS (2025) · cites this paper as [45]

    The Introduction reports MATR3 mutations in people with ALS and FTD and identifies other genes implicated in both conditions, supporting the shared-genetics part of the claim. It also reports TDP-43 pathology in ALS, but does not specifically establish that the shared genetics demonstrate a close overlap between ALS and FTLD-TDP. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Up to half of people with ALS demonstrate cognitive impairment reminiscent of FTLD, while ~1/3 of those with FTLD show motor neuron disease that is indistinguishable from ALS.

    “In addition, up to half of people with ALS demonstrate cognitive impairment reminiscent of FTLD, while ~1/3 of those with FTLD show motor neuron disease that is indistinguishable from ALS (3, 45).”

    From Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS (2025) · cites this paper as [45]

    The Introduction (page unavailable) notes that MATR3 mutations have been found in individuals with both ALS and frontotemporal dementia, supporting a general clinical overlap. It does not report cognitive impairment in up to half of people with ALS, motor neuron disease in about one-third of people with FTLD, or the claimed clinical equivalence. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 76

  1. Arai T Hasegawa M Akiyama H Ikeda K Nonaka T Mori H Mann D Tsuchiya K Yoshida M Hashizume Y Oda T 2006 TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis Biochemical and Biophysical Research Communications 351 602 611 10.1016/j.bbrc.2006.10.093 17084815 · DOI · Paper page
  2. Arrasate M Finkbeiner S 2005 Automated microscope system for determining factors that predict neuronal fate PNAS 102 3840 3845 10.1073/pnas.0409777102 15738408 PMC553329 · DOI
  3. Arrasate M Mitra S Schweitzer ES Segal MR Finkbeiner S 2004 Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death Nature 431 805 810 10.1038/nature02998 15483602 · DOI · Paper page
  4. Barmada SJ Finkbeiner S 2010a Pathogenic TARDBP mutations in amyotrophic lateral sclerosis and frontotemporal dementia: disease-associated pathways Reviews in the Neurosciences 21 251 272 10.1515/REVNEURO.2010.21.4.251 21086759 · DOI
  5. Barmada SJ Ju S Arjun A Batarse A Archbold HC Peisach D Li X Zhang Y Tank EM Qiu H Huang EJ Ringe D Petsko GA Finkbeiner S 2015 Amelioration of toxicity in neuronal models of amyotrophic lateral sclerosis by hUPF1 PNAS 112 7821 7826 10.1073/pnas.1509744112 26056265 PMC4485101 · DOI · Paper page
  6. Barmada SJ Serio A Arjun A Bilican B Daub A Ando DM Tsvetkov A Pleiss M Li X Peisach D Shaw C Chandran S Finkbeiner S 2014 Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models Nature Chemical Biology 10 677 685 10.1038/nchembio.1563 24974230 PMC4106236 · DOI · Paper page
  7. Barmada SJ Skibinski G Korb E Rao EJ Wu JY Finkbeiner S 2010b Cytoplasmic mislocalization of TDP-43 is toxic to neurons and enhanced by a mutation associated with familial amyotrophic lateral sclerosis Journal of Neuroscience 30 639 649 10.1523/JNEUROSCI.4988-09.2010 20071528 PMC2821110 · DOI · Paper page
  8. Belgrader P Dey R Berezney R 1991 Molecular cloning of matrin 3. A 125-kilodalton protein of the nuclear matrix contains an extensive acidic domain The Journal of Biological Chemistry 266 9893 9899 2033075
  9. Boehringer A Garcia-Mansfield K Singh G Bakkar N Pirrotte P Bowser R 2017 ALS associated mutations in matrin 3 alter Protein-Protein interactions and impede mRNA nuclear export Scientific Reports 7 1 14 10.1038/s41598-017-14924-6 29109432 PMC5674072 · DOI
  10. Brayer KJ Kulshreshtha S Segal DJ 2008 The protein-binding potential of C2H2 zinc finger domains Cell Biochemistry and Biophysics 51 9 19 10.1007/s12013-008-9007-6 18286240 · DOI
  11. Burdach J O'Connell MR Mackay JP Crossley M 2012 Two-timing zinc finger transcription factors liaising with RNA Trends in Biochemical Sciences 37 199 205 10.1016/j.tibs.2012.02.001 22405571 · DOI
  12. Christensen E 1987 Multivariate survival analysis using Cox's regression model Hepatology 7 1346 1358 10.1002/hep.1840070628 3679094 · DOI
  13. Chudakov DM Lukyanov S Lukyanov KA 2007 Tracking intracellular protein movements using photoswitchable fluorescent proteins PS-CFP2 and Dendra2 Nature Protocols 2 2024 2032 10.1038/nprot.2007.291 17703215 · DOI
  14. Coelho MB Attig J Bellora N König J Hallegger M Kayikci M Eyras E Ule J Smith CW 2015 Nuclear matrix protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB The EMBO Journal 34 653 668 10.15252/embj.201489852 25599992 PMC4365034 · DOI
  15. Conicella AE Zerze GH Mittal J Fawzi NL 2016 ALS mutations disrupt phase separation mediated by α-Helical structure in the TDP-43 Low-Complexity C-Terminal domain Structure 24 1537 1549 10.1016/j.str.2016.07.007 27545621 PMC5014597 · DOI
  16. Daigle JG Lanson NA Smith RB Casci I Maltare A Monaghan J Nichols CD Kryndushkin D Shewmaker F Pandey UB 2013 RNA-binding ability of FUS regulates neurodegeneration, cytoplasmic mislocalization and incorporation into stress granules associated with FUS carrying ALS-linked mutations Human Molecular Genetics 22 1193 1205 10.1093/hmg/dds526 23257289 PMC3578413 · DOI
  17. Dormann D Rodde R Edbauer D Bentmann E Fischer I Hruscha A Than ME Mackenzie IR Capell A Schmid B Neumann M Haass C 2010 ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import The EMBO Journal 29 2841 2857 10.1038/emboj.2010.143 20606625 PMC2924641 · DOI · Paper page
  18. Dreser A Vollrath JT Sechi A Johann S Roos A Yamoah A Katona I Bohlega S Wiemuth D Tian Y Schmidt A Vervoorts J Dohmen M Beyer C Anink J Aronica E Troost D Weis J Goswami A 2017 The ALS-linked E102Q mutation in sigma receptor-1 leads to ER stress-mediated defects in protein homeostasis and dysregulation of RNA-binding proteins Cell Death and Differentiation 24 1655 1671 10.1038/cdd.2017.88 28622300 PMC5596426 · DOI
  19. Elden AC Kim HJ Hart MP Chen-Plotkin AS Johnson BS Fang X Armakola M Geser F Greene R Lu MM Padmanabhan A Clay-Falcone D McCluskey L Elman L Juhr D Gruber PJ Rüb U Auburger G Trojanowski JQ Lee VM Van Deerlin VM Bonini NM Gitler AD 2010 Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS Nature 466 1069 1075 10.1038/nature09320 20740007 PMC2965417 · DOI
  20. Erickson HP 2009 Size and shape of protein molecules at the nanometer level determined by sedimentation, gel filtration, and electron microscopy Biological Procedures Online 11 32 51 10.1007/s12575-009-9008-x 19495910 PMC3055910 · DOI · Paper page
  21. Fecto F Yan J Vemula SP Liu E Yang Y Chen W Zheng JG Shi Y Siddique N Arrat H Donkervoort S Ajroud-Driss S Sufit RL Heller SL Deng HX Siddique T 2011 SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis Archives of Neurology 68 1440 1446 10.1001/archneurol.2011.250 22084127 · DOI · Paper page
  22. Feit H Silbergleit A Schneider LB Gutierrez JA Fitoussi RP Réyès C Rouleau GA Brais B Jackson CE Beckmann JS Seboun E 1998 Vocal cord and pharyngeal weakness with autosomal dominant distal myopathy: clinical description and gene localization to 5q31 The American Journal of Human Genetics 63 1732 1742 10.1086/302166 9837826 PMC1377645 · DOI
  23. Gallego-Iradi MC Clare AM Brown HH Janus C Lewis J Borchelt DR 2015 Subcellular localization of matrin 3 containing mutations associated with ALS and distal myopathy PLoS One 10 e0142144 10.1371/journal.pone.0142144 26528920 PMC4631352 · DOI
  24. Goldstein L Trescott OH 1970 Characterization of RNAs that do and do not migrate between cytoplasm and nucleus PNAS 67 1367 1374 10.1073/pnas.67.3.1367 5274464 PMC283361 · DOI
  25. Gopal PP Nirschl JJ Klinman E Holzbaur EL 2017 Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons PNAS 114 E2466 E2475 10.1073/pnas.1614462114 28265061 PMC5373408 · DOI
  26. Gupta R Lan M Mojsilovic-Petrovic J Choi WH Safren N Barmada S Lee MJ Kalb R 2017 The proline/Arginine dipeptide from hexanucleotide repeat expanded C9ORF72 inhibits the proteasome Eneuro 4 ENEURO.0249-16.2017 10.1523/ENEURO.0249-16.2017 28197542 PMC5282547 · DOI
  27. Hibino Y Ohzeki H Hirose N Sugano N 1998 Involvement of phosphorylation in binding of nuclear scaffold proteins from rat liver to a highly repetitive DNA component Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1396 88 96 10.1016/S0167-4781(97)00176-0 9524232 · DOI
  28. Hibino Y Ohzeki H Sugano N Hiraga K 2000 Transcription modulation by a rat nuclear scaffold protein, P130, and a rat highly repetitive DNA component or various types of animal and plant matrix or scaffold attachment regions Biochemical and Biophysical Research Communications 279 282 287 10.1006/bbrc.2000.3938 11112453 · DOI
  29. Hibino Y Usui T Morita Y Hirose N Okazaki M Sugano N Hiraga K 2006 Molecular properties and intracellular localization of rat liver nuclear scaffold protein P130 Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1759 195 207 10.1016/j.bbaexp.2006.04.010 16814881 · DOI
  30. Hisada-Ishii S Ebihara M Kobayashi N Kitagawa Y 2007 Bipartite nuclear localization signal of matrin 3 is essential for vertebrate cells Biochemical and Biophysical Research Communications 354 72 76 10.1016/j.bbrc.2006.12.191 17223080 · DOI
  31. Hocking LJ Lucas GJ Daroszewska A Mangion J Olavesen M Cundy T Nicholson GC Ward L Bennett ST Wuyts W Van Hul W Ralston SH 2002 Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget's disease Human Molecular Genetics 11 2735 2739 10.1093/hmg/11.22.2735 12374763 · DOI · Paper page
  32. Igaz LM Kwong LK Lee EB Chen-Plotkin A Swanson E Unger T Malunda J Xu Y Winton MJ Trojanowski JQ Lee VM Vm-y L 2011 Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice Journal of Clinical Investigation 121 726 738 10.1172/JCI44867 21206091 PMC3026736 · DOI
  33. Ihara R Matsukawa K Nagata Y Kunugi H Tsuji S Chihara T Kuranaga E Miura M Wakabayashi T Hashimoto T Iwatsubo T 2013 RNA binding mediates neurotoxicity in the transgenic Drosophila model of TDP-43 proteinopathy Human Molecular Genetics 22 4474 4484 10.1093/hmg/ddt296 23804749 · DOI
  34. Inagaki H Matsushima Y Nakamura K Ohshima M Kadowaki T Kitagawa Y 1996 A large DNA-binding nuclear protein with RNA recognition motif and serine/arginine-rich domain Journal of Biological Chemistry 271 12525 12531 10.1074/jbc.271.21.12525 8647861 · DOI
  35. Iradi MCG Triplett JC Thomas JD Davila R Crown AM Brown H Lewis J Swanson MS Xu G Rodriguez-Lebron E Borchelt DR 2018 Characterization of gene regulation and protein interaction networks for Matrin 3 encoding mutations linked to amyotrophic lateral sclerosis and myopathy Scientific Reports 8 4049 10.1038/s41598-018-21371-4 29511296 PMC5840295 · DOI
  36. Johnson BS McCaffery JM Lindquist S Gitler AD 2008 A yeast TDP-43 proteinopathy model: exploring the molecular determinants of TDP-43 aggregation and cellular toxicity PNAS 105 6439 6444 10.1073/pnas.0802082105 18434538 PMC2359814 · DOI
  37. Johnson BS Snead D Lee JJ McCaffery JM Shorter J Gitler AD 2009 TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity Journal of Biological Chemistry 284 20329 20339 10.1074/jbc.M109.010264 19465477 PMC2740458 · DOI
  38. Johnson JO Mandrioli J Benatar M Abramzon Y Van Deerlin VM Trojanowski JQ Gibbs JR Brunetti M Gronka S Wuu J Ding J McCluskey L Martinez-Lage M Falcone D Hernandez DG Arepalli S Chong S Schymick JC Rothstein J Landi F Wang YD Calvo A Mora G Sabatelli M Monsurrò MR Battistini S Salvi F Spataro R Sola P Borghero G Galassi G Scholz SW Taylor JP Restagno G Chiò A Traynor BJ ITALSGEN Consortium 2010 Exome sequencing reveals VCP mutations as a cause of familial ALS Neuron 68 857 864 10.1016/j.neuron.2010.11.036 21145000 PMC3032425 · DOI · Paper page
  39. Johnson JO Pioro EP Boehringer A Chia R Feit H Renton AE Pliner HA Abramzon Y Marangi G Winborn BJ Gibbs JR Nalls MA Morgan S Shoai M Hardy J Pittman A Orrell RW Malaspina A Sidle KC Fratta P Harms MB Baloh RH Pestronk A Weihl CC Rogaeva E Zinman L Drory VE Borghero G Mora G Calvo A Rothstein JD Drepper C Sendtner M Singleton AB Taylor JP Cookson MR Restagno G Sabatelli M Bowser R Chiò A Traynor BJ ITALSGEN 2014 Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis Nature Neuroscience 17 664 666 10.1038/nn.3688 24686783 PMC4000579 · DOI
  40. Kabashi E Valdmanis PN Dion P Spiegelman D McConkey BJ Vande Velde C Bouchard JP Lacomblez L Pochigaeva K Salachas F Pradat PF Camu W Meininger V Dupre N Rouleau GA 2008 TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis Nature Genetics 40 572 574 10.1038/ng.132 18372902 · DOI · Paper page
  41. Kalderon D Roberts BL Richardson WD Smith AE 1984 A short amino acid sequence able to specify nuclear location Cell 39 499 509 10.1016/0092-8674(84)90457-4 6096007 · DOI
  42. Kim HJ Kim NC Wang YD Scarborough EA Moore J Diaz Z MacLea KS Freibaum B Li S Molliex A Kanagaraj AP Carter R Boylan KB Wojtas AM Rademakers R Pinkus JL Greenberg SA Trojanowski JQ Traynor BJ Smith BN Topp S Gkazi AS Miller J Shaw CE Kottlors M Kirschner J Pestronk A Li YR Ford AF Gitler AD Benatar M King OD Kimonis VE Ross ED Weihl CC Shorter J Taylor JP 2013 Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS Nature 495 467 473 10.1038/nature11922 23455423 PMC3756911 · DOI
  43. Kimonis VE Fulchiero E Vesa J Watts G 2008 VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: review of a unique disorder Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1782 744 748 10.1016/j.bbadis.2008.09.003 18845250 · DOI
  44. Klar J Sobol M Melberg A Mäbert K Ameur A Johansson AC Feuk L Entesarian M Orlén H Casar-Borota O Dahl N 2013 Welander distal myopathy caused by an ancient founder mutation in TIA1 associated with perturbed splicing Human Mutation 34 572 577 10.1002/humu.22282 23348830 · DOI
  45. Kwiatkowski TJ Bosco DA Leclerc AL Tamrazian E Vanderburg CR Russ C Davis A Gilchrist J Kasarskis EJ Munsat T Valdmanis P Rouleau GA Hosler BA Cortelli P de Jong PJ Yoshinaga Y Haines JL Pericak-Vance MA Yan J Ticozzi N Siddique T McKenna-Yasek D Sapp PC Horvitz HR Landers JE Brown RH 2009 Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis Science 323 1205 1208 10.1126/science.1166066 19251627 · DOI
  46. Leblond CS Gan-Or Z Spiegelman D Laurent SB Szuto A Hodgkinson A Dionne-Laporte A Provencher P de Carvalho M Orrù S Brunet D Bouchard JP Awadalla P Dupré N Dion PA Rouleau GA 2016 Replication study of MATR3 in familial and sporadic amyotrophic lateral sclerosis Neurobiology of Aging 37 209.e17 209.e21 10.1016/j.neurobiolaging.2015.09.013 26493020 · DOI
  47. Lin KP Tsai PC Liao YC Chen WT Tsai CP Soong BW Lee YC 2015a Mutational analysis of MATR3 in Taiwanese patients with amyotrophic lateral sclerosis Neurobiology of Aging 36 2005.e1 2005.e4 10.1016/j.neurobiolaging.2015.02.008 25771394 · DOI
  48. Lin Y Protter DS Rosen MK Parker R 2015b Formation and maturation of Phase-Separated liquid droplets by RNA-Binding proteins Molecular Cell 60 208 219 10.1016/j.molcel.2015.08.018 26412307 PMC4609299 · DOI
  49. Mackenzie IR Nicholson AM Sarkar M Messing J Purice MD Pottier C Annu K Baker M Perkerson RB Kurti A Matchett BJ Mittag T Temirov J Hsiung GR Krieger C Murray ME Kato M Fryer JD Petrucelli L Zinman L Weintraub S Mesulam M Keith J Zivkovic SA Hirsch-Reinshagen V Roos RP Züchner S Graff-Radford NR Petersen RC Caselli RJ Wszolek ZK Finger E Lippa C Lacomis D Stewart H Dickson DW Kim HJ Rogaeva E Bigio E Boylan KB Taylor JP Rademakers R 2017 TIA1 mutations in amyotrophic lateral sclerosis and frontotemporal dementia promote phase separation and alter stress granule dynamics Neuron 95 808 816 10.1016/j.neuron.2017.07.025 28817800 PMC5576574 · DOI
  50. Maharana S Wang J Papadopoulos DK Richter D Pozniakovsky A Poser I Bickle M Rizk S Guillén-Boixet J Franzmann TM Jahnel M Marrone L Chang YT Sterneckert J Tomancak P Hyman AA Alberti S 2018 RNA buffers the phase separation behavior of prion-like RNA binding proteins Science 360 918 921 10.1126/science.aar7366 29650702 PMC6091854 · DOI
  51. Marangi G Lattante S Doronzio PN Conte A Tasca G Monforte M Patanella AK Bisogni G Meleo E La Spada S Zollino M Sabatelli M 2017 Matrin 3 variants are frequent in Italian ALS patients Neurobiology of Aging 49 218.e1 218.e7 10.1016/j.neurobiolaging.2016.09.023 28029397 · DOI
  52. Millecamps S De Septenville A Teyssou E Daniau M Camuzat A Albert M LeGuern E Galimberti D Brice A Marie Y Le Ber I Ber L French research network on FTD and FTD-ALS 2014 Genetic analysis of matrin 3 gene in French amyotrophic lateral sclerosis patients and frontotemporal lobar degeneration with amyotrophic lateral sclerosis patients Neurobiology of Aging 35 2882.e13 2882.e15 10.1016/j.neurobiolaging.2014.07.016 25158920 · DOI
  53. Miller J Arrasate M Shaby BA Mitra S Masliah E Finkbeiner S 2010 Quantitative relationships between huntingtin levels, polyglutamine length, inclusion body formation, and neuronal death provide novel insight into huntington's disease molecular pathogenesis Journal of Neuroscience 30 10541 10550 10.1523/JNEUROSCI.0146-10.2010 20685997 PMC3078518 · DOI
  54. Molliex A Temirov J Lee J Coughlin M Kanagaraj AP Kim HJ Mittag T Taylor JP 2015 Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization Cell 163 123 133 10.1016/j.cell.2015.09.015 26406374 PMC5149108 · DOI
  55. Moloney C Rayaprolu S Howard J Fromholt S Brown H Collins M Cabrera M Duffy C Siemienski Z Miller D Swanson MS Notterpek L Borchelt DR Lewis J 2016 Transgenic mice overexpressing the ALS-linked protein Matrin 3 develop a profound muscle phenotype Acta Neuropathologica Communications 4 1 12 10.1186/s40478-016-0393-5 27863507 PMC5116203 · DOI
  56. Monahan Z Ryan VH Janke AM Burke KA Rhoads SN Zerze GH O'Meally R Dignon GL Conicella AE Zheng W Best RB Cole RN Mittal J Shewmaker F Fawzi NL 2017 Phosphorylation of the FUS low-complexity domain disrupts phase separation, aggregation, and toxicity The EMBO Journal 36 2951 2967 10.15252/embj.201696394 28790177 PMC5641905 · DOI
  57. Murray DT Kato M Lin Y Thurber KR Hung I McKnight SL Tycko R 2017 Structure of FUS protein fibrils and its relevance to self-assembly and phase separation of low-complexity domains Cell 171 615 627 10.1016/j.cell.2017.08.048 28942918 PMC5650524 · DOI
  58. Neumann M Sampathu DM Kwong LK Truax AC Micsenyi MC Chou TT Bruce J Schuck T Grossman M Clark CM McCluskey LF Miller BL Masliah E Mackenzie IR Feldman H Feiden W Kretzschmar HA Trojanowski JQ Lee VM Vm-y L 2006 Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis Science 314 130 133 10.1126/science.1134108 17023659 · DOI · Paper page
  59. Origone P Verdiani S Bandettini Di Poggio M Zuccarino R Vignolo M Caponnetto C Mandich P 2015 A novel Arg147Trp MATR3 missense mutation in a slowly progressive ALS Italian patient Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration 16 530 531 10.3109/21678421.2015.1058397 26199109 · DOI
  60. Patel A Lee HO Jawerth L Maharana S Jahnel M Hein MY Stoynov S Mahamid J Saha S Franzmann TM Pozniakovski A Poser I Maghelli N Royer LA Weigert M Myers EW Grill S Drechsel D Hyman AA Alberti S 2015 A Liquid-to-Solid phase transition of the ALS protein FUS accelerated by disease mutation Cell 162 1066 1077 10.1016/j.cell.2015.07.047 26317470 · DOI
  61. Peng K Radivojac P Vucetic S Dunker AK Obradovic Z 2006 Length-dependent prediction of protein intrinsic disorder BMC Bioinformatics 7 208 10.1186/1471-2105-7-208 16618368 PMC1479845 · DOI
  62. Qiu H Lee S Shang Y Wang WY Au KF Kamiya S Barmada SJ Finkbeiner S Lui H Carlton CE Tang AA Oldham MC Wang H Shorter J Filiano AJ Roberson ED Tourtellotte WG Chen B Tsai LH Huang EJ 2014 ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects Journal of Clinical Investigation 124 981 999 10.1172/JCI72723 24509083 PMC3938263 · DOI
  63. Quintero-Rivera F Xi QJ Keppler-Noreuil KM Lee JH Higgins AW Anchan RM Roberts AE Seong IS Fan X Lage K Lu LY Tao J Hu X Berezney R Gelb BD Kamp A Moskowitz IP Lacro RV Lu W Morton CC Gusella JF Maas RL 2015 MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus Human Molecular Genetics 24 2375 2389 10.1093/hmg/ddv004 25574029 PMC4380077 · DOI
  64. Rajgor D Hanley JG Shanahan CM 2016 Identification of novel nesprin-1 binding partners and cytoplasmic matrin-3 in processing bodies Molecular Biology of the Cell 27 3894 3902 10.1091/mbc.e16-06-0346 27733621 PMC5170611 · DOI
  65. Salton M Elkon R Borodina T Davydov A Yaspo ML Halperin E Shiloh Y 2011 Matrin 3 binds and stabilizes mRNA PLoS ONE 6 e23882 10.1371/journal.pone.0023882 21858232 PMC3157474 · DOI
  66. Salton M Lerenthal Y Wang SY Chen DJ Shiloh Y 2010 Involvement of Matrin 3 and SFPQ/NONO in the DNA damage response Cell Cycle 9 1568 1576 10.4161/cc.9.8.11298 20421735 · DOI
  67. Saudou F Finkbeiner S Devys D Greenberg ME 1998 Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions Cell 95 55 66 10.1016/S0092-8674(00)81782-1 9778247 · DOI
  68. Senderek J Garvey SM Krieger M Guergueltcheva V Urtizberea A Roos A Elbracht M Stendel C Tournev I Mihailova V Feit H Tramonte J Hedera P Crooks K Bergmann C Rudnik-Schöneborn S Zerres K Lochmüller H Seboun E Weis J Beckmann JS Hauser MA Jackson CE 2009 Autosomal-dominant distal myopathy associated with a recurrent missense mutation in the gene encoding the nuclear matrix protein, matrin 3 The American Journal of Human Genetics 84 511 518 10.1016/j.ajhg.2009.03.006 19344878 PMC2667977 · DOI
  69. Shin Y Brangwynne CP 2017 Liquid phase condensation in cell physiology and disease Science 357 eaaf4382 10.1126/science.aaf4382 28935776 · DOI
  70. Tada M Doi H Koyano S Kubota S Fukai R Hashiguchi S Hayashi N Kawamoto Y Kunii M Tanaka K Takahashi K Ogawa Y Iwata R Yamanaka S Takeuchi H Tanaka F 2018 Matrin 3 is a component of neuronal cytoplasmic inclusions of motor neurons in sporadic amyotrophic lateral sclerosis The American Journal of Pathology 188 507 514 10.1016/j.ajpath.2017.10.007 29128563 · DOI
  71. Taylor JP Brown RH Cleveland DW 2016 Decoding ALS: from genes to mechanism Nature 539 197 206 10.1038/nature20413 27830784 PMC5585017 · DOI
  72. Ticozzi N Vance C Leclerc AL Keagle P Glass JD McKenna-Yasek D Sapp PC Silani V Bosco DA Shaw CE Brown RH Landers JE 2011 Mutational analysis reveals the FUS homolog TAF15 as a candidate gene for familial amyotrophic lateral sclerosis American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 156B 285 290 10.1002/ajmg.b.31158 21438137 · DOI
  73. Uemura Y Oshima T Yamamoto M Reyes CJ Costa Cruz PH Shibuya T Kawahara Y 2017 Matrin3 binds directly to intronic pyrimidine-rich sequences and controls alternative splicing Genes to Cells 22 785 798 10.1111/gtc.12512 28695676 · DOI
  74. Vance C Rogelj B Hortobágyi T De Vos KJ Nishimura AL Sreedharan J Hu X Smith B Ruddy D Wright P Ganesalingam J Williams KL Tripathi V Al-Saraj S Al-Chalabi A Leigh PN Blair IP Nicholson G de Belleroche J Gallo JM Miller CC Shaw CE 2009 Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6 Science 323 1208 1211 10.1126/science.1165942 19251628 PMC4516382 · DOI
  75. Xu L Li J Tang L Zhang N Fan D 2016 MATR3 mutation analysis in a Chinese cohort with sporadic amyotrophic lateral sclerosis Neurobiology of Aging 38 218.e3 218.e4 10.1016/j.neurobiolaging.2015.11.023 26708275 · DOI
  76. Zhang Z Carmichael GG 2001 The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs Cell 106 465 476 10.1016/S0092-8674(01)00466-4 11525732 · DOI

Cited by

Sorted by citations

Authors
Malik, A. M., Miguez, R. A., Li, X., Ho, Y.-S., Feldman, E. L., & Barmada, S. J.
Affiliations
  • University of Michigan (US)
  • Wayne State University (US)
Corresponding author
Barmada, Sami J
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2018-07-17
Volume
7
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.35977
PMC
PMC6050042
OpenAlex
W2951485368
Cited by
92
References
0
Citations by year
2026: 4 · 2025: 8 · 2024: 13 · 2023: 16 · 2022: 10 · 2021: 13 · 2020: 15 · 2019: 11 · 2018: 2
FWCI
6.95
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of Neurological Disorders and Stroke (NS097542)
  • University of Michigan
  • National Institute on Aging (AG053760)
  • National Institute of General Medical Sciences (GM007863)
  • A. Alfred Taubman Medical Research Institute
  • Program for Neurology Research and Discovery
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
MATR3, amyotrophic lateral sclerosis, frontotemporal dementia, RNA-binding proteins, neurotoxicity, nucleocytoplasmic localization, zinc finger, RNA recognition motif, liquid-like droplets, pathogenic variants, sporadic ALS, primary neurons, neurodegeneration
MeSH terms
RNA Recognition Motif, Animals, Cell Nucleus, Cell Survival, Humans, Models, Biological, Mutation, Nerve Degeneration, Neurons, Neurotoxins, Nucleic Acids, Protein Binding, Solubility, Zinc Fingers, RNA-Binding Proteins, Rats, Long-Evans, Nuclear Matrix-Associated Proteins, Mutant Proteins, Rats, Protein Stability, HEK293 Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review