Frameshift peptides alter the properties of truncated FUS proteins in ALS-FUS

An, Haiyan, Rabesahala de Meritens, Camille, Buchman, Vladimir L ORCID: https://orcid.org/0000-0002-7631-8352 and Shelkovnikova, Tatyana A ORCID: https://orcid.org/0000-0003-1367-5309 2020. Frameshift peptides alter the properties of truncated FUS proteins in ALS-FUS. Molecular Brain 13 , 77. 10.1186/s13041-020-00618-0

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Abstract

Mutations in the FUS gene cause a subset of ALS cases (ALS-FUS). The majority of FUS mutations are missense mutations affecting the nuclear localisation signal (NLS) of FUS. In addition, a number of frameshift mutations which result in complete NLS deletion have been described. Patients bearing frameshift mutations usually present with more aggressive disease, characterised by an early onset and rapid progression. Both missense mutations in the NLS coding sequence and complete loss of the NLS are known to result in cytoplasmic mislocalisation of FUS protein. However, in addition to the removal of FUS functional domains, frameshift mutations in most cases lead to the attachment of a “tail” of novel amino acids at the FUS C-terminus – a frameshift peptide. It is not clear whether these peptide tails would affect the properties of truncated FUS proteins. In the current study, we compared intracellular behaviour of disease-associated truncated FUS proteins with and without the corresponding frameshift peptides. We demonstrate that some of these peptides can affect subcellular distribution and/or increase aggregation capacity and stability of the truncated FUS protein. Our study suggests that frameshift peptides can alter the properties of truncated FUS variants which may modulate FUS pathogenicity and contribute to the variability of the disease course in ALS-FUS.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	BioMed Central
ISSN:	1756-6606
Date of First Compliant Deposit:	29 April 2020
Date of Acceptance:	29 April 2020
Last Modified:	05 May 2023 00:16
URI:	https://orca.cardiff.ac.uk/id/eprint/131311

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