The RNA-binding protein MARTA2 regulates dendritic targeting of MAP2 mRNAs in rat neurons

Authors


  • Data deposition: The MARTA2 cDNA sequence is available under GenBank accession number DQ144645.

Address correspondence and reprint requests to Stefan Kindler, Institute for Human Genetics, University Medical Center Hamburg-Eppendorf, Campus Forschung N27, Martinistr. 52, D-20246 Hamburg, Germany. E-mail: kindler@uke.de

Abstract

Dendritic targeting of mRNAs encoding the microtubule-associated protein 2 (MAP2) in neurons involves a cis-acting dendritic targeting element. Two rat brain proteins, MAP2-RNA trans-acting protein (MARTA)1 and MARTA2, bind to the cis-element with both high affinity and specificity. In this study, affinity-purified MARTA2 was identified as orthologue of human far-upstream element binding protein 3. In neurons, it resides in somatodendritic granules and dendritic spines and associates with MAP2 mRNAs. Expression of a dominant-negative variant of MARTA2 disrupts dendritic targeting of endogenous MAP2 mRNAs, while not noticeably altering the level and subcellular distribution of polyadenylated mRNAs as a whole. Finally, MAP2 transcripts associate with the microtubule-based motor KIF5 and inhibition of KIF5, but not cytoplasmic dynein function disrupts extrasomatic trafficking of MAP2 mRNA granules. Thus, in neurons MARTA2 appears to represent a key trans-acting factor involved in KIF5-mediated dendritic targeting of MAP2 mRNAs.

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