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. 2018 May 2;98(3):495-511.e6.
doi: 10.1016/j.neuron.2018.03.030. Epub 2018 Apr 12.

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

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

Georgi Tushev et al. Neuron. .

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.

Keywords: 3′ UTR; RNA localization; RNA stability; RNA transport; RNA-binding protein; cis-regulatory element; local translation; microRNA; synaptic plasticity; transcriptomics.

Comment in

  • The power of 3' UTRs.
    Bray N. Bray N. Nat Rev Neurosci. 2018 Jun;19(6):319. doi: 10.1038/s41583-018-0011-6. Nat Rev Neurosci. 2018. PMID: 29740172 No abstract available.

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