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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.
