title: ALS Along the Axons - Expression of Coding and Noncoding RNA Differs in Axons of ALS models.
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 SOD1G93Aand 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.
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Nimrod
authors.initials: N
authors.lastname: Rotem
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Iddo
authors.initials: I
authors.lastname: Magen
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Ionescu
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Noga
authors.initials: N
authors.lastname: Gershoni-Emek
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Topaz
authors.initials: T
authors.lastname: Altman
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medicine, Burke Medical Research Institute, White Plains, NY, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Costa
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Gradus
authors.affiliation: Bioinformatics Unit, G.S.W. Faculty of Life Sciences, Tel-Aviv University, Israel.
authors.forename: Metsada
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medicine, Burke Medical Research Institute, White Plains, NY, USA.
authors.forename: Dianna E
authors.initials: DE
authors.lastname: Willis
authors.affiliation: Department of Nephrology and Hypertension, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Iddo Z
authors.initials: IZ
authors.lastname: Ben-Dov
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Hornstein
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Perlson
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration; D022661:RNA, Untranslated / Q000235:genetics; D000072105:Superoxide Dismutase-1 / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D022661:RNA, Untranslated; C000606290:SOD1 protein, human; C000598624:TARDBP protein, human; D000072105:Superoxide Dismutase-1