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Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation

View ORCID ProfileTamsin J. Samuels, Yoav Arava, View ORCID ProfileAino I. Järvelin, View ORCID ProfileFrancesca Robertson, Jeffrey Y. Lee, Lu Yang, Ching-Po Yang, View ORCID ProfileTzumin Lee, View ORCID ProfileDavid Ish-Horowicz, View ORCID ProfileIlan Davis
doi: https://doi.org/10.1101/135848
Tamsin J. Samuels
1Department of Biochemistry, The University of Oxford, UK
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Yoav Arava
1Department of Biochemistry, The University of Oxford, UK
2Technion, Haifa, Israel
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Aino I. Järvelin
1Department of Biochemistry, The University of Oxford, UK
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Francesca Robertson
1Department of Biochemistry, The University of Oxford, UK
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Jeffrey Y. Lee
1Department of Biochemistry, The University of Oxford, UK
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Lu Yang
1Department of Biochemistry, The University of Oxford, UK
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Ching-Po Yang
3Janelia Research Campus, Virginia, USA
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Tzumin Lee
3Janelia Research Campus, Virginia, USA
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David Ish-Horowicz
1Department of Biochemistry, The University of Oxford, UK
4MRC Laboratory for Molecular Cell Biology, University College, London, UK
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Ilan Davis
1Department of Biochemistry, The University of Oxford, UK
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  • For correspondence: ilan.davis@bioch.ox.ac.uk
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ABSTRACT

During Drosophila and vertebrate brain development, the conserved transcription factor Prospero/Prox1 is an important regulator of the transition between proliferation and differentiation. Prospero level is low in neural stem cells and their immediate progeny, but is upregulated in larval neurons and it is unknown how this process is controlled. Here, we use single molecule fluorescent in situ hybridisation to show that larval neurons selectively transcribe a long prospero mRNA isoform containing a 15 kb 3’ untranslated region, which is bound in the brain by the conserved RNA-binding protein Syncrip/hnRNPQ. Syncrip binding increases the mRNA stability of the long prospero isoform, which allows an upregulation of Prospero protein production. Our findings highlight a regulatory strategy involving alternative polyadenylation followed by differential post-transcriptional regulation.

Footnotes

  • In this manuscript, we report that Prospero protein levels are regulated through mRNA stability, depending on the RNA binding protein, Syncrip, and the inclusion of an extremely long pros 3 UTR. In the original version of the manuscript we used a nonsense-mediated mRNA decay mutant to remove the long isoform of pros, and reported that the neuroblasts in the line did not terminate correctly. However, we later discovered that the proslong isoform was unaffected in the mutant and a stock contamination was responsible for our results. Therefore, the results previously described in Figures 3 E,G,I and 6 are invalid. We have now produced an alternative transgenic line, using a transcriptional terminator to remove the long isoform of pros. The new proslong mutant terminates pupal neuroblast division normally. As a consequence, we have refocused the paper on the regulation of Prospero level in larval neurons. This substantial change to the paper involves a new title, many updated figures (with improved four-colour imaging of protein and mRNA) and the removal of data that are no longer relevant to the story.

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Posted November 26, 2019.
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Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation
Tamsin J. Samuels, Yoav Arava, Aino I. Järvelin, Francesca Robertson, Jeffrey Y. Lee, Lu Yang, Ching-Po Yang, Tzumin Lee, David Ish-Horowicz, Ilan Davis
bioRxiv 135848; doi: https://doi.org/10.1101/135848
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Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation
Tamsin J. Samuels, Yoav Arava, Aino I. Järvelin, Francesca Robertson, Jeffrey Y. Lee, Lu Yang, Ching-Po Yang, Tzumin Lee, David Ish-Horowicz, Ilan Davis
bioRxiv 135848; doi: https://doi.org/10.1101/135848

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