title: MicroRNA let-7d regulates the TLX/microRNA-9 cascade to control neural cell fate and neurogenesis.
abstract: MicroRNAs have important functions in the nervous system through post-transcriptional regulation of neurogenesis genes. Here we show that microRNA let-7d, which has been implicated in cocaine addiction and other neurological disorders, targets the neural stem cell regulator TLX. Overexpression of let-7d in vivo reduced neural stem cell proliferation and promoted premature neuronal differentiation and migration, a phenotype similar to those induced by TLX knockdown or overexpression of its negatively-regulated target, microRNA-9. We found a let-7d binding sequence in the tlx 3' UTR and demonstrated that let-7d reduced TLX expression levels in neural stem cells, which in turn, up-regulated miR-9 expression. Moreover, co-expression of let-7d and TLX lacking its 3' UTR in vivo restored neural stem cell proliferation and reversed the premature neuronal differentiation and migration. Therefore, manipulating let-7d and its downstream targets could be a novel strategy to unravel neurogenic signaling pathways and identify potential interventions for relevant neurological disorders.
authors: Department of Neurosciences, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd, Duarte, CA 91010, USA.
authors: Chunnian
authors: C
authors: Zhao
authors: GuoQiang
authors: G
authors: Sun
authors: Peng
authors: P
authors: Ye
authors: Shengxiu
authors: S
authors: Li
authors: Yanhong
authors: Y
authors: Shi
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001921:Brain / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D004285:Dogs; D007519:Isoantigens / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D010641:Phenotype; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D007519:Isoantigens; C551804:MIRN9 microRNA, mouse; D035683:MicroRNAs; D034741:RNA, Small Interfering; C542687:mirnlet7 microRNA, mouse; C055067:trophoblast-lymphocyte cross-reactive antigens