ELAV and FNE Determine Neuronal Transcript Signatures through EXon-Activated 
Rescue

Carrasco, Judit; Rauer, Michael; Hummel, Barbara; Grzejda, Dominika; Alfonso-Gonzalez, Carlos; Lee, Yeon; Wang, Qingqing; Puchalska, Monika; Mittler, Gerhard; Hilgers, Valérie

doi:10.1016/j.molcel.2020.09.011

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ELAV and FNE Determine Neuronal Transcript Signatures through EXon-Activated Rescue

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Carrasco, Judit
Department Independent Research Groups, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Rauer, Michael
Department Independent Research Groups, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hummel, Barbara
Department Independent Research Groups, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Grzejda, Dominika
Department Independent Research Groups, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Alfonso-Gonzalez, Carlos
Department Independent Research Groups, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Puchalska, Monika
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Mittler, Gerhard
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Hilgers, Valérie
Department Independent Research Groups, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.sciencedirect.com/science/article/abs/pii/S1097276520306195?via%3Dihub
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Citation

Carrasco, J., Rauer, M., Hummel, B., Grzejda, D., Alfonso-Gonzalez, C., Lee, Y., et al. (2020). ELAV and FNE Determine Neuronal Transcript Signatures through EXon-Activated Rescue. Molecular Cell, 80, 156-163. doi:10.1016/j.molcel.2020.09.011.

Cite as: https://hdl.handle.net/21.11116/0000-0007-70EA-3

Abstract

The production of alternative RNA variants contributes to the tissue-specific regulation of gene expression. In the animal nervous system, a systematic shift toward distal sites of transcription termination produces transcript signatures that are crucial for neuron development and function. Here, we report that, in Drosophila, the highly conserved protein ELAV globally regulates all sites of neuronal 3' end processing and directly binds to proximal polyadenylation sites of target mRNAs in vivo. We uncover an endogenous strategy of functional gene rescue that safeguards neuronal RNA signatures in an ELAV loss-of-function context. When not directly repressed by ELAV, the transcript encoding the ELAV paralog FNE acquires a mini-exon, generating a new protein able to translocate to the nucleus and rescue ELAV-mediated alternative polyadenylation and alternative splicing. We propose that exon-activated functional rescue is a more widespread mechanism that ensures robustness of processes regulated by a hierarchy, rather than redundancy, of effectors.