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

• Published in: Journal of neurochemistry Vol. 124; no. 5; pp. 670 - 684
• Main Authors: Zivraj, Krishna H., Rehbein, Monika, Ölschläger‐Schütt, Janin, Schob, Claudia, Falley, Katrin, Buck, Friedrich, Schweizer, Michaela, Schepis, Antonino, Kremmer, Elisabeth, Richter, Dietmar, Kreienkamp, Hans‐Jürgen, Kindler, Stefan
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.03.2013
• Subjects: Animals; Blotting, Western; Dendrites - metabolism; Dendrites - ultrastructure; Immunohistochemistry; Immunoprecipitation; In Situ Hybridization; kinesin; Mass Spectrometry; Microscopy, Immunoelectron; microtubule; Microtubule-Associated Proteins - metabolism; molecular motor; Neurons - metabolism; Neurons - ultrastructure; Protein Transport - physiology; Rats; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; ribonucleoprotein particle; RNA transport; RNA, Messenger - metabolism; RNA-Binding Proteins - metabolism; trans‐acting factor
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.12079

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. MARTA2 selects MAP2 mRNAs for dendritic targeting Targeting of select neuronal mRNAs into dendrites requires recognition of a cis‐acting element by a trans‐acting RNA‐binding protein. Here MARTA2 was identified as selective trans‐factor mediating dendritic trafficking of MAP2 mRNAs, but not αCamKII, β‐actin or Shank1 transcripts. Thus, different neuronal mRNAs employ distinct molecular dendritic targeting mechanisms.