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Hum Genet. 2017 Sep;136(9):1193-1214. doi: 10.1007/s00439-017-1830-7. Epub 2017 Jul 31.

Genetic mutations in RNA-binding proteins and their roles in ALS.

Author information

1
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117593, Singapore.
2
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, 92093, USA.
3
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117593, Singapore. geneyeo@ucsd.edu.
4
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, 92093, USA. geneyeo@ucsd.edu.
5
Molecular Engineering Laboratory, A*STAR, Singapore, 138673, Singapore. geneyeo@ucsd.edu.

Abstract

Mutations in genes that encode RNA-binding proteins (RBPs) have emerged as critical determinants of neurological diseases, especially motor neuron disorders such as amyotrophic lateral sclerosis (ALS). RBPs are involved in all aspects of RNA processing, controlling the life cycle of RNAs from synthesis to degradation. Hallmark features of RBPs in neuron dysfunction include misregulation of RNA processing, mislocalization of RBPs to the cytoplasm, and abnormal aggregation of RBPs. Much progress has been made in understanding how ALS-associated mutations in RBPs drive pathogenesis. Here, we focus on several key RBPs involved in ALS-TDP-43, HNRNP A2/B1, HNRNP A1, FUS, EWSR1, and TAF15-and review our current understanding of how mutations in these proteins cause disease.

PMID:
28762175
PMCID:
PMC5602095
DOI:
10.1007/s00439-017-1830-7
[Indexed for MEDLINE]
Free PMC Article

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