標題: Mir-17 similar to 92 Governs Motor Neuron Subtype Survival by Mediating Nuclear PTEN
作者: Tung, Ying-Tsen
Lu, Ya-Lin
Peng, Kuan-Chih
Yen, Ya-Ping
Chang, Mien
Li, Joye
Jung, Heekyung
Thams, Sebastian
Huang, Yuan-Ping
Hung, Jui-Hung
Chen, Jun-An
生物科技學系
Department of Biological Science and Technology
公開日期: 26-May-2015
摘要: Motor neurons (MNs) are unique because they project their axons outside of the CNS to innervate the peripheral muscles. Limb-innervating lateral motor column MNs (LMC-MNs) travel substantially to innervate distal limb mesenchyme. How LMC-MNs fine-tune the balance between survival and apoptosis while wiring the sensorimotor circuit en route remains unclear. Here, we show that the mir-17 similar to 92 cluster is enriched in embryonic stem cell (ESC)derived LMC-MNs and that conditional mir-17 similar to 92 deletion in MNs results in the death of LMC-MNs in vitro and in vivo. mir-17 similar to 92 overexpression rescues MNs from apoptosis, which occurs spontaneously during embryonic development. PTEN is a primary target of mir-17 similar to 92 responsible for LMC-MN degeneration. Additionally, mir-17 similar to 92 directly targets components of E3 ubiquitin ligases, affecting PTEN subcellular localization through monoubiquitination. This miRNA-mediated regulation modulates both target expression and target subcellular localization, providing LMC-MNs with an intricate defensive mechanism that controls their survival.
URI: http://dx.doi.org/10.1016/j.celrep.2015.04.050
http://hdl.handle.net/11536/124803
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2015.04.050
期刊: CELL REPORTS
Volume: 11
Issue: 8
起始頁: 1305
結束頁: 1318
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