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Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):E4995-5004. doi: 10.1073/pnas.1513780112. Epub 2015 Aug 24.

Positive feedback between RNA-binding protein HuD and transcription factor SATB1 promotes neurogenesis.

Author information

1
Waisman Center and Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705; State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China;
2
Waisman Center and Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705;
3
Department of Neurosciences, University of New Mexico, Albuquerque, NM 87131; nbizzozero@salud.unm.edu wxguo@genetics.ac.cn xinyu.zhao@wisc.edu.
4
Waisman Center and Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705; State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China nbizzozero@salud.unm.edu wxguo@genetics.ac.cn xinyu.zhao@wisc.edu.
5
Waisman Center and Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705; nbizzozero@salud.unm.edu wxguo@genetics.ac.cn xinyu.zhao@wisc.edu.

Abstract

The mammalian embryonic lethal abnormal vision (ELAV)-like protein HuD is a neuronal RNA-binding protein implicated in neuronal development, plasticity, and diseases. Although HuD has long been associated with neuronal development, the functions of HuD in neural stem cell differentiation and the underlying mechanisms have gone largely unexplored. Here we show that HuD promotes neuronal differentiation of neural stem/progenitor cells (NSCs) in the adult subventricular zone by stabilizing the mRNA of special adenine-thymine (AT)-rich DNA-binding protein 1 (SATB1), a critical transcriptional regulator in neurodevelopment. We find that SATB1 deficiency impairs the neuronal differentiation of NSCs, whereas SATB1 overexpression rescues the neuronal differentiation phenotypes resulting from HuD deficiency. Interestingly, we also discover that SATB1 is a transcriptional activator of HuD during NSC neuronal differentiation. In addition, we demonstrate that NeuroD1, a neuronal master regulator, is a direct downstream target of SATB1. Therefore, HuD and SATB1 form a positive regulatory loop that enhances NeuroD1 transcription and subsequent neuronal differentiation. Our results here reveal a novel positive feedback network between an RNA-binding protein and a transcription factor that plays critical regulatory roles in neurogenesis.

KEYWORDS:

HuD; NeuroD1; SATB1; neural stem cells; neurogenesis

PMID:
26305964
PMCID:
PMC4568658
DOI:
10.1073/pnas.1513780112
[Indexed for MEDLINE]
Free PMC Article

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