Publication Date:
2015-12-19
Description:
Dysfunction of microRNA (miRNA) metabolism is thought to underlie diseases affecting motoneurons. One miRNA, miR-218, is abundantly and selectively expressed by developing and mature motoneurons. Here we show that mutant mice lacking miR-218 die neonatally and exhibit neuromuscular junction defects, motoneuron hyperexcitability, and progressive motoneuron cell loss, all of which are hallmarks of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Gene profiling reveals that miR-218 modestly represses a cohort of hundreds of genes that are neuronally enriched but are not specific to a single neuron subpopulation. Thus, the set of messenger RNAs targeted by miR-218, designated TARGET(218), defines a neuronal gene network that is selectively tuned down in motoneurons to prevent neuromuscular failure and neurodegeneration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amin, Neal D -- Bai, Ge -- Klug, Jason R -- Bonanomi, Dario -- Pankratz, Matthew T -- Gifford, Wesley D -- Hinckley, Christopher A -- Sternfeld, Matthew J -- Driscoll, Shawn P -- Dominguez, Bertha -- Lee, Kuo-Fen -- Jin, Xin -- Pfaff, Samuel L -- F31-NS080340-03/NS/NINDS NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- P30 NS072031/NS/NINDS NIH HHS/ -- R01AG0476669/AG/NIA NIH HHS/ -- R01GM088278/GM/NIGMS NIH HHS/ -- R01NS044420/NS/NINDS NIH HHS/ -- R01NS054154/NS/NINDS NIH HHS/ -- R01NS060833/NS/NINDS NIH HHS/ -- R21NS084254/NS/NINDS NIH HHS/ -- T32-GM007198/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1525-9. doi: 10.1126/science.aad2509.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Medical Scientist Training Program, University of California, San Diego (UCSD), 9500 Gilman Drive, La Jolla, CA 92037, USA. Biomedical Sciences Graduate Program, UCSD, 9500 Gilman Drive, La Jolla, CA 92037, USA. ; Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ; Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ; Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Medical Scientist Training Program, University of California, San Diego (UCSD), 9500 Gilman Drive, La Jolla, CA 92037, USA. Neurosciences Graduate Program, UCSD, 9500 Gilman Drive, La Jolla, CA 92037, USA. ; Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Biological Sciences Graduate Program, UCSD, 9500 Gilman Drive, La Jolla, CA 92037, USA. ; Peptide Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ; Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. pfaff@salk.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680198" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Gene Expression Regulation
;
Gene Regulatory Networks
;
Mice
;
Mice, Knockout
;
MicroRNAs/genetics/*physiology
;
Motor Neuron Disease/*genetics/physiopathology
;
Motor Neurons/metabolism/pathology/*physiology
;
Neurodegenerative Diseases/*genetics/pathology
;
Spinal Cord/metabolism/physiopathology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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