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Sci Rep. 2017 Mar 16;7:44500. doi: 10.1038/srep44500.

ALS Along the Axons - Expression of Coding and Noncoding RNA Differs in Axons of ALS models.

Author information

1
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
2
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
3
Brain and Mind Research Institute, Weill Cornell Medicine, Burke Medical Research Institute, White Plains, NY, USA.
4
Bioinformatics Unit, G.S.W. Faculty of Life Sciences, Tel-Aviv University, Israel.
5
Department of Nephrology and Hypertension, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Abstract

Amyotrophic lateral sclerosis (ALS) is a multifactorial lethal motor neuron disease with no known treatment. Although the basic mechanism of its degenerative pathogenesis remains poorly understood, a subcellular spatial alteration in RNA metabolism is thought to play a key role. The nature of these RNAs remains elusive, and a comprehensive characterization of the axonal RNAs involved in maintaining neuronal health has yet to be described. Here, using cultured spinal cord (SC) neurons grown using a compartmented platform followed by next-generation sequencing (NGS) technology, we find that RNA expression differs between the somatic and axonal compartments of the neuron, for both mRNA and microRNA (miRNA). Further, the introduction of SOD1G93A and TDP43A315T, established ALS-related mutations, changed the subcellular expression and localization of RNAs within the neurons, showing a spatial specificity to either the soma or the axon. Altogether, we provide here the first combined inclusive profile of mRNA and miRNA expression in two ALS models at the subcellular level. These data provide an important resource for studies on the roles of local protein synthesis and axon degeneration in ALS and can serve as a possible target pool for ALS treatment.

PMID:
28300211
PMCID:
PMC5353576
DOI:
10.1038/srep44500
[Indexed for MEDLINE]
Free PMC Article

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