Analysis of nuclear export sequence regions of FUS-related RNA-binding proteins in Essential tremor

Oswaldo Lorenzo-Betancor, Kotaro Ogaki, Alexandra Soto-Ortolaza, Catherine Labbé, Carles Vilariño Gü Ell, Alex Rajput, Ali H. Rajput, Pau Pastor, Sara Ortega, Elena Lorenzo, Audrey J. Strongosky, Jay A Van Gerpen, Ryan J. Uitti, Zbigniew K Wszolek, Owen A Ross

Research output: Contribution to journalArticle

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Abstract

Background and Objective: Genes encoding RNA-binding proteins, including FUS and TDP43, play a central role in different neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Recently, a mutation located in the nuclear export signal (NES) of the FUS gene has been reported to cause an autosomal dominant form of familial Essential tremor.

Material and Methods: We sequenced the exons coding the NES domains of five RNA-binding proteins (TARDBP, hnRNPA2B1, hnRNPA1, TAF15 and EWSR1) that have been previously implicated in neurodegeneration in a series of 257 essential tremor (ET) cases and 376 healthy controls. We genotyped 404 additional ET subjects and 510 healthy controls to assess the frequency of the EWSR1 p.R471C substitution.

Results: We identified a rare EWSR1 p.R471C substitution, which is highly conserved, in a single subject with familial ET. The pathogenicity of this substitution remains equivocal, as DNA samples from relatives were not available and the genotyping of 404 additional ET subjects did not reveal any further carriers. No other variants were observed with significant allele frequency differences compared to controls in the NES coding regions.

Conclusions: The present study demonstrates that the NES domains of RNA-binding proteins are highly conserved. The role of the EWSR1 p.R471C substitution needs to be further evaluated in future studies.

Original languageEnglish (US)
Article numbere111989
JournalPLoS One
Volume9
Issue number11
DOIs
StatePublished - Nov 6 2014

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RNA-Binding Protein FUS
Essential Tremor
RNA-binding proteins
RNA-Binding Proteins
Cell Nucleus Active Transport
Nuclear Export Signals
Substitution reactions
Neurodegenerative diseases
Gene encoding
neurodegenerative diseases
genotyping
exons
gene frequency
Exons
Frontotemporal Lobar Degeneration
pathogenicity
genes
Genes
mutation
Amyotrophic Lateral Sclerosis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lorenzo-Betancor, O., Ogaki, K., Soto-Ortolaza, A., Labbé, C., Ell, C. V. G., Rajput, A., ... Ross, O. A. (2014). Analysis of nuclear export sequence regions of FUS-related RNA-binding proteins in Essential tremor. PLoS One, 9(11), [e111989]. https://doi.org/10.1371/journal.pone.0111989

Analysis of nuclear export sequence regions of FUS-related RNA-binding proteins in Essential tremor. / Lorenzo-Betancor, Oswaldo; Ogaki, Kotaro; Soto-Ortolaza, Alexandra; Labbé, Catherine; Ell, Carles Vilariño Gü; Rajput, Alex; Rajput, Ali H.; Pastor, Pau; Ortega, Sara; Lorenzo, Elena; Strongosky, Audrey J.; Van Gerpen, Jay A; Uitti, Ryan J.; Wszolek, Zbigniew K; Ross, Owen A.

In: PLoS One, Vol. 9, No. 11, e111989, 06.11.2014.

Research output: Contribution to journalArticle

Lorenzo-Betancor, O, Ogaki, K, Soto-Ortolaza, A, Labbé, C, Ell, CVG, Rajput, A, Rajput, AH, Pastor, P, Ortega, S, Lorenzo, E, Strongosky, AJ, Van Gerpen, JA, Uitti, RJ, Wszolek, ZK & Ross, OA 2014, 'Analysis of nuclear export sequence regions of FUS-related RNA-binding proteins in Essential tremor', PLoS One, vol. 9, no. 11, e111989. https://doi.org/10.1371/journal.pone.0111989
Lorenzo-Betancor O, Ogaki K, Soto-Ortolaza A, Labbé C, Ell CVG, Rajput A et al. Analysis of nuclear export sequence regions of FUS-related RNA-binding proteins in Essential tremor. PLoS One. 2014 Nov 6;9(11). e111989. https://doi.org/10.1371/journal.pone.0111989
Lorenzo-Betancor, Oswaldo ; Ogaki, Kotaro ; Soto-Ortolaza, Alexandra ; Labbé, Catherine ; Ell, Carles Vilariño Gü ; Rajput, Alex ; Rajput, Ali H. ; Pastor, Pau ; Ortega, Sara ; Lorenzo, Elena ; Strongosky, Audrey J. ; Van Gerpen, Jay A ; Uitti, Ryan J. ; Wszolek, Zbigniew K ; Ross, Owen A. / Analysis of nuclear export sequence regions of FUS-related RNA-binding proteins in Essential tremor. In: PLoS One. 2014 ; Vol. 9, No. 11.
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AU - Labbé, Catherine

AU - Ell, Carles Vilariño Gü

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