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  Alternative 3' UTRs Modify the Localization, Regulatory Potential, Stability, and Plasticity of mRNAs in Neuronal Compartments

Tushev, G., Glock, C., Heumuller, M., Biever, A., Jovanovic, M., & Schuman, E. M. (2018). Alternative 3' UTRs Modify the Localization, Regulatory Potential, Stability, and Plasticity of mRNAs in Neuronal Compartments. Neuron, 98(3), 495-511 e6. doi:10.1016/j.neuron.2018.03.030.

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Tushev, G., Author
Glock, C., Author
Heumuller, M., Author
Biever, A., Author
Jovanovic, M., Author
Schuman, Erin M.1, Author              
Affiliations:
1Synaptic Plasticity Department, Max Planck Institute for Brain Research, Max Planck Society, ou_2461710              

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Free keywords: 3' Untranslated Regions/*physiology Animals Animals, Newborn Cells, Cultured HEK293 Cells Hippocampus/chemistry/metabolism Humans Male Neuronal Plasticity/*physiology Neurons/chemistry/*metabolism Protein Isoforms/chemistry/metabolism Protein Stability RNA, Messenger/analysis/*metabolism Rats Rats, Sprague-Dawley *3' utr *RNA localization *RNA stability *RNA transport *RNA-binding protein *cis-regulatory element *local translation *microRNA *synaptic plasticity *transcriptomics
 Abstract: Neurons localize mRNAs near synapses where their translation can be regulated by synaptic demand and activity. Differences in the 3' UTRs of mRNAs can change their localization, stability, and translational regulation. Using 3' end RNA sequencing of microdissected rat brain slices, we discovered a huge diversity in mRNA 3' UTRs, with many transcripts showing enrichment for a particular 3' UTR isoform in either somata or the neuropil. The 3' UTR isoforms of localized transcripts are significantly longer than the 3' UTRs of non-localized transcripts and often code for proteins associated with axons, dendrites, and synapses. Surprisingly, long 3' UTRs add not only new, but also duplicate regulatory elements. The neuropil-enriched 3' UTR isoforms have significantly longer half-lives than somata-enriched isoforms. Finally, the 3' UTR isoforms can be significantly altered by enhanced activity. Most of the 3' UTR plasticity is transcription dependent, but intriguing examples of changes that are consistent with altered stability, trafficking between compartments, or local "remodeling" remain.

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 Dates: 2018-04-17
 Publication Status: Published in print
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 Identifiers: Other: 29656876
DOI: 10.1016/j.neuron.2018.03.030
ISSN: 1097-4199 (Electronic)0896-6273 (Linking)
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Title: Neuron
Source Genre: Journal
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Pages: - Volume / Issue: 98 (3) Sequence Number: - Start / End Page: 495 - 511 e6 Identifier: -