Protein kinase KIS localizes to RNA granules and enhances local translation.
The regulation of mRNA transport is a fundamental process for cytoplasmic sorting of transcripts and spatially controlled translational derepression once properly localized. There is growing evidence that translation is locally modulated as a result of specific synaptic inputs. However, the underlying molecular mechanisms that regulate this translational process are just ... emerging. We show that KIS, a serine/threonine kinase functionally related to microtubule dynamics and axon development, interacts with three proteins found in RNA granules: KIF3A, NonO, and eEF1A. KIS localizes to RNA granules and colocalizes with the KIF3A kinesin and the beta-actin mRNA in cultured cortical neurons. In addition, KIS is found associated with KIF3A and 10 RNP-transported mRNAs in brain extracts. The results of knockdown experiments indicate that KIS is required for normal neurite outgrowth. More important, the kinase activity of KIS stimulates 3' untranslated region-dependent local translation in neuritic projections. We propose that KIS is a component of the molecular device that modulates translation in RNA-transporting granules as a result of local signals.
Mesh Terms:
3' Untranslated Regions, Actins, Animals, Cell Line, Cerebral Cortex, Cytoplasmic Granules, Gene Expression Regulation, Humans, Intracellular Signaling Peptides and Proteins, Kinesin, Mice, Neurites, Neurons, Protein Binding, Protein Biosynthesis, Protein Transport, Protein-Serine-Threonine Kinases, RNA, RNA Transport, RNA, Messenger, Ribonucleoproteins, Tissue Extracts
3' Untranslated Regions, Actins, Animals, Cell Line, Cerebral Cortex, Cytoplasmic Granules, Gene Expression Regulation, Humans, Intracellular Signaling Peptides and Proteins, Kinesin, Mice, Neurites, Neurons, Protein Binding, Protein Biosynthesis, Protein Transport, Protein-Serine-Threonine Kinases, RNA, RNA Transport, RNA, Messenger, Ribonucleoproteins, Tissue Extracts
Mol Cell Biol
Date: Feb. 01, 2009
PubMed ID: 19015237
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