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Biophysics Reports 2018, 4(4): 204-214 https://doi.org/10.1007/s41048-018-0066-y
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PTB/nPTB: master regulators of neuronal fate in mammals

Show Author's Information Jing Hu1,  Hao Qian1,  Yuanchao Xue2( ),  Xiang-Dong Fu1,2( )
Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, CA 92093-0651, USA
Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Keywords:
MicroRNA, Polypyrimidine tract-binding proteins, Auto- and cross-regulation of alternative splicing, Neuronal fate determination
Cite this article:
Hu J, Qian H, Xue Y, et al. PTB/nPTB: master regulators of neuronal fate in mammals. Biophysics Reports, 2018, 4(4): 204-214. https://doi.org/10.1007/s41048-018-0066-y
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Abstract Full text About this article

PTB was initially discovered as a polypyrimidine tract-binding protein (hence the name), which corresponds to a specific RNA-binding protein associated with heterogeneous ribonucleoprotein particle (hnRNP I). The PTB family consists of three members in mammalian genomes, with PTBP1 (PTB) expressed in most cell types, PTBP2 (also known as nPTB or brPTB) exclusively found in the nervous system, and PTBP3 (also known as ROD1) predominately detected in immune cells. During neural development, PTB is down-regulated, which induces nPTB, and the expression of both PTB and nPTB becomes diminished when neurons mature. This programed switch, which largely takes place at the splicing level, is critical for the development of the nervous system, with PTB playing a central role in neuronal induction and nPTB guarding neuronal maturation. Remarkably, sequential knockdown of PTB and nPTB has been found to be necessary and sufficient to convert non-neuronal cells to the neuronal lineage. These findings, coupled with exquisite understanding of the molecular circuits regulated by these RNA-binding proteins, establish a critical foundation for their future applications in regenerative medicine.


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PTB/nPTB: master regulators of neuronal fate in mammals

Show Author's information Jing Hu1, Hao Qian1, Yuanchao Xue2( ), Xiang-Dong Fu1,2( )
Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, CA 92093-0651, USA
Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China

Abstract

PTB was initially discovered as a polypyrimidine tract-binding protein (hence the name), which corresponds to a specific RNA-binding protein associated with heterogeneous ribonucleoprotein particle (hnRNP I). The PTB family consists of three members in mammalian genomes, with PTBP1 (PTB) expressed in most cell types, PTBP2 (also known as nPTB or brPTB) exclusively found in the nervous system, and PTBP3 (also known as ROD1) predominately detected in immune cells. During neural development, PTB is down-regulated, which induces nPTB, and the expression of both PTB and nPTB becomes diminished when neurons mature. This programed switch, which largely takes place at the splicing level, is critical for the development of the nervous system, with PTB playing a central role in neuronal induction and nPTB guarding neuronal maturation. Remarkably, sequential knockdown of PTB and nPTB has been found to be necessary and sufficient to convert non-neuronal cells to the neuronal lineage. These findings, coupled with exquisite understanding of the molecular circuits regulated by these RNA-binding proteins, establish a critical foundation for their future applications in regenerative medicine.

Keywords: MicroRNA, Polypyrimidine tract-binding proteins, Auto- and cross-regulation of alternative splicing, Neuronal fate determination

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Publication history

Received: 08 July 2018
Accepted: 21 July 2018
Published: 28 August 2018
Issue date: August 2018

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© The Author(s) 2018

Acknowledgements

This work was supported by grants from the National Key R&D Program of China (2017YFA0504400) and National Institutes of Health of the US (GM049369 and HG004659).

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