title: Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits.
abstract: The induction of pluripotency or trans-differentiation of one cell type to another can be accomplished with cell-lineage-specific transcription factors. Here, we report that repression of a single RNA binding polypyrimidine-tract-binding (PTB) protein, which occurs during normal brain development via the action of miR-124, is sufficient to induce trans-differentiation of fibroblasts into functional neurons. Besides its traditional role in regulated splicing, we show that PTB has a previously undocumented function in the regulation of microRNA functions, suppressing or enhancing microRNA targeting by competitive binding on target mRNA or altering local RNA secondary structure. A key event during neuronal induction is the relief of PTB-mediated blockage of microRNA action on multiple components of the REST complex, thereby derepressing a large array of neuronal genes, including miR-124 and multiple neuronal-specific transcription factors, in nonneuronal cells. This converts a negative feedback loop to a positive one to elicit cellular reprogramming to the neuronal lineage.
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors: Yuanchao
authors: Y
authors: Xue
authors: Kunfu
authors: K
authors: Ouyang
authors: Jie
authors: J
authors: Huang
authors: Yu
authors: Y
authors: Zhou
authors: Hong
authors: H
authors: Ouyang
authors: Hairi
authors: H
authors: Li
authors: Gang
authors: G
authors: Wang
authors: Qijia
authors: Q
authors: Wu
authors: Chaoliang
authors: C
authors: Wei
authors: Yanzhen
authors: Y
authors: Bi
authors: Li
authors: L
authors: Jiang
authors: Zhiqiang
authors: Z
authors: Cai
authors: Hui
authors: H
authors: Sun
authors: Kang
authors: K
authors: Zhang
authors: Yi
authors: Y
authors: Zhang
authors: Ju
authors: J
authors: Chen
authors: Xiang-Dong
authors: XD
authors: Fu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing; D013569:Synapses
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D038941:Polypyrimidine Tract-Binding Protein