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The piRNA pathway sustains adult neurogenesis by repressing protein synthesis

View ORCID ProfileC. Gasperini, R. Pelizzoli, A. Lo Van, D. Mangoni, R.M. Cossu, G. Pascarella, P. Bianchini, P. Bielefeld, M. Scarpato, M. Pons-Espinal, R. Sanges, A. Diaspro, C.P. Fitzsimons, View ORCID ProfileP. Carninci, S. Gustincich, View ORCID ProfileD De Pietri Tonelli
doi: https://doi.org/10.1101/2020.09.15.297739
C. Gasperini
1Neurobiology of miRNA Laboratory, Istituto Italiano di Tecnologia, Genova (Italy)
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  • ORCID record for C. Gasperini
R. Pelizzoli
1Neurobiology of miRNA Laboratory, Istituto Italiano di Tecnologia, Genova (Italy)
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A. Lo Van
1Neurobiology of miRNA Laboratory, Istituto Italiano di Tecnologia, Genova (Italy)
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D. Mangoni
2Central RNA Laboratory, Istituto Italiano di Tecnologia, Genova, (Italy)
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R.M. Cossu
2Central RNA Laboratory, Istituto Italiano di Tecnologia, Genova, (Italy)
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G. Pascarella
3Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama (Japan)
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P. Bianchini
4Nanoscopy, CHT Erzelli, Istituto Italiano di Tecnologia, Genoa (Italy)
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P. Bielefeld
5Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam (The Netherlands)
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M. Scarpato
2Central RNA Laboratory, Istituto Italiano di Tecnologia, Genova, (Italy)
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M. Pons-Espinal
1Neurobiology of miRNA Laboratory, Istituto Italiano di Tecnologia, Genova (Italy)
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R. Sanges
2Central RNA Laboratory, Istituto Italiano di Tecnologia, Genova, (Italy)
6Area of Neuroscience, SISSA, Trieste (Italy)
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A. Diaspro
3Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama (Japan)
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C.P. Fitzsimons
5Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam (The Netherlands)
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P. Carninci
4Nanoscopy, CHT Erzelli, Istituto Italiano di Tecnologia, Genoa (Italy)
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S. Gustincich
2Central RNA Laboratory, Istituto Italiano di Tecnologia, Genova, (Italy)
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D De Pietri Tonelli
1Neurobiology of miRNA Laboratory, Istituto Italiano di Tecnologia, Genova (Italy)
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  • For correspondence: davide.depietri@iit.it
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Abstract

In specific niches of the adult mammalian brain, neural progenitor cells (aNPCs) ensure lifelong neurogenesis. Proper regulation of this process entails important implications for brain plasticity and health. We report that Piwil2 (Mili) and PIWI-interacting RNAs (piRNAs) are abundantly expressed in aNPCs but depleted in their progeny in the adult mouse hippocampus. Loss of function of the piRNA pathway in aNPCs inhibited neurogenesis and increased reactive gliogenesis in vivo and in vitro. PiRNA pathway depletion in cultured aNPCs increased levels of 5S ribosomal RNA, transfer RNAs and mRNAs encoding regulators of translation, resulting in higher polyribosome density and protein synthesis upon differentiation. We propose that the piRNA pathway sustains adult neurogenesis by repressing translation in aNPCs.

One sentence summary The piRNA pathway is enriched in neural precursors and essential for appropriate neurogenesis by modulating translation

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 15, 2020.
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The piRNA pathway sustains adult neurogenesis by repressing protein synthesis
C. Gasperini, R. Pelizzoli, A. Lo Van, D. Mangoni, R.M. Cossu, G. Pascarella, P. Bianchini, P. Bielefeld, M. Scarpato, M. Pons-Espinal, R. Sanges, A. Diaspro, C.P. Fitzsimons, P. Carninci, S. Gustincich, D De Pietri Tonelli
bioRxiv 2020.09.15.297739; doi: https://doi.org/10.1101/2020.09.15.297739
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The piRNA pathway sustains adult neurogenesis by repressing protein synthesis
C. Gasperini, R. Pelizzoli, A. Lo Van, D. Mangoni, R.M. Cossu, G. Pascarella, P. Bianchini, P. Bielefeld, M. Scarpato, M. Pons-Espinal, R. Sanges, A. Diaspro, C.P. Fitzsimons, P. Carninci, S. Gustincich, D De Pietri Tonelli
bioRxiv 2020.09.15.297739; doi: https://doi.org/10.1101/2020.09.15.297739

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