title: miRNA malfunction causes spinal motor neuron disease.
abstract: Defective RNA metabolism is an emerging mechanism involved in ALS pathogenesis and possibly in other neurodegenerative disorders. Here, we show that microRNA (miRNA) activity is essential for long-term survival of postmitotic spinal motor neurons (SMNs) in vivo. Thus, mice that do not process miRNA in SMNs exhibit hallmarks of spinal muscular atrophy (SMA), including sclerosis of the spinal cord ventral horns, aberrant end plate architecture, and myofiber atrophy with signs of denervation. Furthermore, a neurofilament heavy subunit previously implicated in motor neuron degeneration is specifically up-regulated in miRNA-deficient SMNs. We demonstrate that the heavy neurofilament subunit is a target of miR-9, a miRNA that is specifically down-regulated in a genetic model of SMA. These data provide evidence for miRNA function in SMN diseases and emphasize the potential role of miR-9-based regulatory mechanisms in adult neurons and neurodegenerative states.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Haramati
authors.forename: Elik
authors.initials: E
authors.lastname: Chapnik
authors.forename: Yehezkel
authors.initials: Y
authors.lastname: Sztainberg
authors.forename: Raya
authors.initials: R
authors.lastname: Eilam
authors.forename: Raaya
authors.initials: R
authors.lastname: Zwang
authors.forename: Noga
authors.initials: N
authors.lastname: Gershoni
authors.forename: Edwina
authors.initials: E
authors.lastname: McGlinn
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Heiser
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Wills
authors.forename: Itzhak
authors.initials: I
authors.lastname: Wirguin
authors.forename: Lee L
authors.initials: LL
authors.lastname: Rubin
authors.forename: Hidemi
authors.initials: H
authors.lastname: Misawa
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Tabin
authors.forename: Robert
authors.initials: R
authors.lastname: Brown
authors.forename: Alon
authors.initials: A
authors.lastname: Chen
authors.forename: Eran
authors.initials: E
authors.lastname: Hornstein
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009121:Muscle Denervation; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000503:physiopathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D016019:Survival Analysis
chemical_list: C551804:MIRN9 microRNA, mouse; D035683:MicroRNAs; D016900:Neurofilament Proteins; D021122:Protein Subunits; D043244:Ribonuclease III