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EMBO Rep. 2017 Oct;18(10):1762-1774. doi: 10.15252/embr.201744334. Epub 2017 Aug 1.

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

Author information

1
Division of Cell Biology, Biomedical Center, LMU Munich, Martinsried, Germany.
2
Department of Molecular Neuroscience, University College London Institute of Neurology, London, UK.
3
The Francis Crick Institute, London, UK.
4
DK RNA Biology, M.F. Perutz Laboratories, Vienna, Austria.
5
Division of Cell Biology, Biomedical Center, LMU Munich, Martinsried, Germany mkiebler@lmu.de.

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 (Calm3L ) mRNA Calm3L 3'-UTR contains six Stau2 crosslink clusters, four of which are in this retained 3'-UTR intron. The Calm3L 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 Calm3L 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 Calm3L mRNA to distal dendrites.

KEYWORDS:

Calm3; Stau2; intron; neuronal activity; neuronal mRNA regulation

PMID:
28765142
PMCID:
PMC5623867
DOI:
10.15252/embr.201744334
[Indexed for MEDLINE]
Free PMC Article

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