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J. Biol. Chem., Vol. 277, Issue 45, 42701-42705, November 8, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/45/42701    most recent M206635200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ge, W. Articles by Cañete-Soler, R. Search for Related Content PubMed PubMed Citation Articles by Ge, W. Articles by Cañete-Soler, R. Social Bookmarking                      What's this?

Binding of p190RhoGEF to a Destabilizing Element on the Light Neurofilament mRNA Is Competed by BC1 RNA^*

Weiwen Ge, Junhua Wu, Jinbin Zhai, Zhenying Nie, Hong Lin, William W. Schlaepfer, and Rafaela Cañete-Soler

From the Division of Neuropathology, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104-6100

The enhancement of RNA-mediated motor neuron degeneration in transgenic mice by mutating a major mRNA instability determinant in a light neurofilament (NF-L) transgene implicates cognate RNA binding factors in the pathogenesis of motor neuron degeneration. p190RhoGEF is a neuron-enriched guanine exchange factor (GEF) that binds to the NF-L-destabilizing element, to c-Jun N-terminal kinase-interactive protein-1 (JIP-1), and to 14-3-3 and may link neurofilament expression to pathways affecting neuronal homeostasis. This study was undertaken to identify additional RNA species that bind p190RhoGEF and could affect interactions of the exchange factor with NF-L transcripts. The C-terminal domain of p190RhoGEF, containing the RNA-binding site, was expressed as a glutathione S-transferase fusion protein and was used as an affinity probe to isolate interactive RNAs in rat brain extracts. As expected, NF-L mRNA was identified as an RNA specie eluted from the affinity column. In addition, BC1 RNA was also found enriched in the bound RNA fraction. BC1 is a 152-nucleotide RNA that is highly expressed but untranslated in differentiated neurons. We show that BC1 and NF-L mRNA bind to a similar site in the C-terminal domain of p190RhoGEF, and their bindings to p190RhoGEF are readily cross-competed. Moreover, we identify a novel binding site in BC1 to account for its interaction with p190RhoGEF. The findings suggest a novel role of BC1 in differentiated neurons involving RNA-protein interactions of p190RhoGEF.

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