TY - JOUR
T1 - Loss of motoneuron-specific microRNA-218 causes systemic neuromuscular failure
AU - Amin, Neal D.
AU - Bai, Ge
AU - Klug, Jason R.
AU - Bonanomi, Dario
AU - Pankratz, Matthew T.
AU - Gifford, Wesley D.
AU - Hinckley, Christopher A.
AU - Sternfeld, Matthew J.
AU - Driscoll, Shawn P.
AU - Dominguez, Bertha
AU - Lee, Kuo Fen
AU - Jin, Xin
AU - Pfaff, Samuel L.
PY - 2015/12/18
Y1 - 2015/12/18
N2 - 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 TARGET218 , defines a neuronal gene network that is selectively tuned down in motoneurons to prevent neuromuscular failure and neurodegeneration.
AB - 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 TARGET218 , defines a neuronal gene network that is selectively tuned down in motoneurons to prevent neuromuscular failure and neurodegeneration.
UR - https://www.scopus.com/pages/publications/84950289897
U2 - 10.1126/science.aad2509
DO - 10.1126/science.aad2509
M3 - 文章
C2 - 26680198
AN - SCOPUS:84950289897
SN - 0036-8075
VL - 350
SP - 1525
EP - 1529
JO - Science
JF - Science
IS - 6267
ER -