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, 41 (9), 818-829

RNA-Binding Proteins in Amyotrophic Lateral Sclerosis


RNA-Binding Proteins in Amyotrophic Lateral Sclerosis

Melody Zhao et al. Mol Cells.


Significant research efforts are ongoing to elucidate the complex molecular mechanisms underlying amyotrophic lateral sclerosis (ALS), which may in turn pinpoint potential therapeutic targets for treatment. The ALS research field has evolved with recent discoveries of numerous genetic mutations in ALS patients, many of which are in genes encoding RNA binding proteins (RBPs), including TDP-43, FUS, ATXN2, TAF15, EWSR1, hnRNPA1, hnRNPA2/B1, MATR3 and TIA1. Accumulating evidence from studies on these ALS-linked RBPs suggests that dysregulation of RNA metabolism, cytoplasmic mislocalization of RBPs, dysfunction in stress granule dynamics of RBPs and increased propensity of mutant RBPs to aggregate may lead to ALS pathogenesis. Here, we review current knowledge of the biological function of these RBPs and the contributions of ALS-linked mutations to disease pathogenesis.

Keywords: ALS; RNA-binding proteins.


Fig. 1
Fig. 1. Functional domains and ALS-linked mutations in RNA binding proteins
The arrowheads indicate single mutations and asterisks denote mutation hotspots found in both familial and sporadic ALS cases. RRM, RNA recognition motif; RGG, arginine/glycine-rich region; Znf, Zinc finger motif; NES, nuclear export signal; NLS, nuclear localization signal; Lsm, like-Sm protein domain; QGSY, glutamine, glycine, serine and tyrosine-rich region; Gly-rich, glycine-rich region; LsmAD, Lsm-associated domain; PAM2, PABP-interacting motif 2; Poly-Q, polyglutamine repeat; a.a., amino acids.

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