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Targeted Intron Retention and Excision for Rapid Gene Regulation in Response to Neuronal Activity

Mauger, Oriane and Lemoine, Frédéric and Scheiffele, Peter. (2016) Targeted Intron Retention and Excision for Rapid Gene Regulation in Response to Neuronal Activity. Neuron, 92 (6). pp. 1266-1278.

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Official URL: http://edoc.unibas.ch/52499/

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Abstract

Activity-dependent transcription has emerged as a major source of gene products that regulate neuronal excitability, connectivity, and synaptic properties. However, the elongation rate of RNA polymerases imposes a significant temporal constraint for transcript synthesis, in particular for long genes where new synthesis requires hours. Here we reveal a novel, transcription-independent mechanism that releases transcripts within minutes of neuronal stimulation. We found that, in the mouse neocortex, polyadenylated transcripts retain select introns and are stably accumulated in the cell nucleus. A subset of these intron retention transcripts undergoes activity-dependent splicing, cytoplasmic export, and ribosome loading, thus acutely releasing mRNAs in response to stimulation. This process requires NMDA receptor- and calmodulin-dependent kinase pathways, and it is particularly prevalent for long transcripts. We conclude that regulated intron retention in fully transcribed RNAs represents a mechanism to rapidly mobilize a pool of mRNAs in response to neuronal activity.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Scheiffele)
UniBasel Contributors:Scheiffele, Peter
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
ISSN:0896-6273
e-ISSN:1097-4199
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Oct 2017 14:51
Deposited On:26 Oct 2017 14:51

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