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A retained intron in the 3'-UTR of Calm3 mRNA mediates its Staufen2- and activity-dependent localization to neuronal dendrites

Item Type:Article
Title:A retained intron in the 3'-UTR of Calm3 mRNA mediates its Staufen2- and activity-dependent localization to neuronal dendrites
Creators Name:Sharangdhar, T. and Sugimoto, Y. and Heraud-Farlow, J. and Fernández-Moya, S.M. and Ehses, J. and Ruiz de Los Mozos, I. and Ule, J. and Kiebler, M.A.
Abstract:Dendritic localization and hence local mRNA translation contributes to synaptic plasticity in neurons. Staufen2 (Stau2) is a well-known neuronal double-stranded RNA-binding protein (dsRBP) that has been implicated in dendritic mRNA localization. The specificity of Stau2 binding to its target mRNAs remains elusive. Using individual-nucleotide resolution CLIP (iCLIP), we identified significantly enriched Stau2 binding to the 3'-UTRs of 356 transcripts. In 28 (7.9%) of those, binding occurred to a retained intron in their 3'-UTR The strongest bound 3'-UTR intron was present in the longest isoform of Calmodulin 3 (Calm3(L)) mRNA Calm3(L) 3'-UTR contains six Stau2 crosslink clusters, four of which are in this retained 3'-UTR intron. The Calm3(L) mRNA localized to neuronal dendrites, while lack of the 3'-UTR intron impaired its dendritic localization. Importantly, Stau2 mediates this dendritic localization via the 3'-UTR intron, without affecting its stability. Also, NMDA-mediated synaptic activity specifically promoted the dendritic mRNA localization of the Calm3(L) isoform, while inhibition of synaptic activity reduced it substantially. Together, our results identify the retained intron as a critical element in recruiting Stau2, which then allows for the localization of Calm3(L) mRNA to distal dendrites.
Keywords:Calm3, Intron, Neuronal Activity, Neuronal mRNA Regulation, Stau2, Animals, Mice, Rats
Source:EMBO Reports
ISSN:1469-221X
Publisher:EMBO Press
Volume:18
Number:10
Page Range:1762-1774
Date:1 October 2017
Official Publication:https://doi.org/10.15252/embr.201744334
PubMed:View item in PubMed

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