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Regulation of miR-34 Family in Neuronal Development

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Abstract

Differentiation of neural stem cells (NSC’s) to mature and functional neurons requires coordinated expression of mRNA, microRNAs (miRNAs) and regulatory proteins. Our earlier unbiased miRNA profiling studies have identified miR-200, miR-34 and miR-221/222 as maximally up-regulated miRNA families in differentiating PC12 cells and demonstrated the capability of miR-200 family in inducing neuronal differentiation (J. Neurochem, 2015, 133, 640–652). In present study, we have investigated role of miR-34 family in neuronal differentiation and identified P53 as mediator of nerve growth factor (NGF) induced miR-34a expression in differentiating PC12 cells. Our studies have shown that NGF induced miR-34a, arrests proliferating PC12 cells to G1 phase, which is pre-requisite for neuronal differentiation. Our studies have also shown that increased expression of miR-34a controls the P53 level in differentiated PC12 cells in feedback inhibition manner, which probably prevents differentiated cells from P53 induced apoptosis. Expression profiling of miR-34 family in different neuronal, non-neuronal and developing cells have identified differentiated and aged brain cells as richest source of miR-34, which also indicates that higher expression of miR-34 family helps in maintaining the mature neurons in non-proliferative stage. In conclusion, our studies have shown that miR-34 is brain enriched miRNA family, which up-regulates with neuronal maturation and brain ageing and co-operative regulation of P53 and miR-34a helps in neuronal differentiation by arresting cells in G1 phase.

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Acknowledgments

Funding for the work carried out in the present study has been provided by CSIR network projects InDepth (BSC0111) and Department of Biotechnology project (GAP-254). Mr. Abhishek Jauhari is grateful to UGC, New Delhi, and Ms. Tanisha Singh is grateful to Department of Science and Technology (DST), New Delhi for providing the research fellowships. The technical assistance of Mr. B S Pandey and Mr. Puneet Khare is also gratefully acknowledged. The CSIR-IITR communication reference number is 3417.

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Authors and Affiliations

  1. Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR- Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226001, India

    Abhishek Jauhari, Tanisha Singh, Parul Singh, Devendra Parmar & Sanjay Yadav

  2. Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, India

    Abhishek Jauhari

  3. Department of Biochemistry, School of Dental Sciences, Babu Banarasi Das University, Lucknow, India

    Tanisha Singh & Parul Singh

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  1. Abhishek Jauhari
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Correspondence to Sanjay Yadav.

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The authors declare that they have no conflicts of interest with the contents of this article.

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Abhishek Jauhari and Tanisha Singh both author’s contributed equally

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Jauhari, A., Singh, T., Singh, P. et al. Regulation of miR-34 Family in Neuronal Development. Mol Neurobiol 55, 936–945 (2018). https://doi.org/10.1007/s12035-016-0359-4

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  • DOI: https://doi.org/10.1007/s12035-016-0359-4

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