Highlights
- •The RNA binding protein hnRNP A1 is dysfunctional in MS.
- •IFNγ contributes to hnRNP A1 dysfunction.
- •Neurons in MS brain show pathogenic features of hnRNP A1 dysfunction.
- •The features include hnRNP A1 nuclear depletion & colocalization in cytoplasmic stress granules.
Abstract
Dysfunction of the RNA binding protein (RBP) heterogeneous nuclear ribonuclear protein
A1 (hnRNP A1) has been shown to contribute to the pathogenesis of neurodegenerative
diseases, but its involvement in multiple sclerosis (MS) is largely unknown. In a
neuronal cell line, interferon-γ caused hnRNP A1 nucleocytoplasmic mislocalization;
colocalization of hnRNP A1 in stress granules (SGs); and inhibition of translation.
Neurons in the brain of a MS patient showed pathogenic RBP dysfunction, including
nuclear depletion of hnRNP A1, its mislocalization to the cytoplasm, and its colocalization
in SGs. These data indicate a role for dysfunctional hnRNP A1 in the pathogenesis
of MS.
Graphical abstract
Graphical Abstract
Keywords
Abbreviations:
ALS (amyotrophic lateral sclerosis), FTLD (frontotemporal lobar degeneration), FUS (fused in sarcoma), hnRNP A1 (heterogeneous nuclear ribonucleoprotein A1), IFNγ (interferon gamma), IL-12 (interleukin-12), MS (Multiple sclerosis), RBP (RNA binding protein), SG (stress granule), TDP-43 (TAR-DNA binding protein 43), TGF-β (transforming growth factor-beta), TIA1 (T-cell restricted intracellular antigen-1)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: August 29, 2018
Accepted:
August 28,
2018
Received in revised form:
August 27,
2018
Received:
August 8,
2018
Identification
Copyright
© 2018 Published by Elsevier B.V.
