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Publication : A nuclear function of Hu proteins as neuron-specific alternative RNA processing regulators.

First Author  Zhu H Year  2006
Journal  Mol Biol Cell Volume  17
Issue  12 Pages  5105-14
PubMed ID  17035636 Mgi Jnum  J:117945
Mgi Id  MGI:3698085 Doi  10.1091/mbc.E06-02-0099
Citation  Zhu H, et al. (2006) A nuclear function of Hu proteins as neuron-specific alternative RNA processing regulators. Mol Biol Cell 17(12):5105-14
abstractText  Recent advances in genome-wide analysis of alternative splicing indicate that extensive alternative RNA processing is associated with many proteins that play important roles in the nervous system. Although differential splicing and polyadenylation make significant contributions to the complexity of the nervous system, our understanding of the regulatory mechanisms underlying the neuron-specific pathways is very limited. Mammalian neuron-specific embryonic lethal abnormal visual-like Hu proteins (HuB, HuC, and HuD) are a family of RNA-binding proteins implicated in neuronal differentiation and maintenance. It has been established that Hu proteins increase expression of proteins associated with neuronal function by up-regulating mRNA stability and/or translation in the cytoplasm. We report here a novel function of these proteins as RNA processing regulators in the nucleus. We further elucidate the underlying mechanism of this regulation. We show that in neuron-like cells, Hu proteins block the activity of TIA-1/TIAR, two previously identified, ubiquitously expressed proteins that promote the nonneuronal pathway of calcitonin/calcitonin gene-related peptide (CGRP) pre-mRNA processing. These studies define not only the first neuron-specific regulator of the calcitonin/CGRP system but also the first nuclear function of Hu proteins.
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