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| Status |
Public on Aug 03, 2015 |
| Title |
Let-7 coordinately suppresses components of the amino acid sensing pathway to induce autophagy |
| Platform organisms |
Homo sapiens; Mus musculus; Rattus norvegicus; Human alphaherpesvirus 1; Human betaherpesvirus 5; human gammaherpesvirus 4; JC polyomavirus; Human immunodeficiency virus 1; Human gammaherpesvirus 8; Betapolyomavirus hominis; Betapolyomavirus macacae |
| Sample organism |
Mus musculus |
| Experiment type |
Non-coding RNA profiling by array
|
| Summary |
Macroautophagy (hereafter autophagy) is the major pathway by which macromolecules and organelles are degraded. Autophagy is regulated by the mTOR signaling pathway, which is the focal point for integration of metabolic information, with mTORC1 playing a central role in balancing biosynthesis and catabolism. Of the various inputs to mTORC1, the amino acid sensing pathway is among the most potent. Based upon transcriptome analysis of neurons subjected to nutrient deprivation, we identified let-7 as a microRNA capable of promoting neuronal autophagy. We found that let-7 activates autophagy by coordinately down-regulating the amino acid sensing pathway to prevent mTORC1 activation. Let-7 induced autophagy in the brain and greatly reduced protein aggregates in a lentivirus model of polyglutamine disease, establishing the physiological relevance of let-7 for in vivo autophagy modulation. Moreover, peripheral delivery of let-7 anti-miR repressed autophagy in muscle and white fat, suggesting that let-7 autophagy regulation extends beyond the CNS. Hence, let-7 plays a central role in nutrient homeostasis and proteostasis regulation in higher organisms.
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| Overall design |
Using sets of wild-type C57BL/6J mice, we established primary cortical neuron cultures from P0 littermates, and cultured these neurons (n = 3 / set) in CM or NLM for 4 hrs.
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| Contributor(s) |
Beyer RP, Dubinsky A |
| Citation(s) |
25295787 |
| |
| Submission date |
Aug 15, 2014 |
| Last update date |
Sep 05, 2017 |
| Contact name |
James William MacDonald |
| E-mail(s) |
jmacdon@uw.edu
|
| Organization name |
University of Washington
|
| Department |
Environmental and Occupational Health Sciences
|
| Street address |
4225 Roosevelt Way NE
|
| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98105-6099 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL7724 |
miRCURY LNA microRNA Array, v. 9.2, all organisms |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA258380 |
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