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Cambray, S, Pedraza, N, Rafel, M, Garí, E, Aldea, M and Gallego, C (2009) Protein kinase KIS localizes to RNA granules and enhances local translation. Mol. Cell. Biol. 29:726-35
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.
3' Untranslated Regions/metabolism; Actins/genetics; Actins/metabolism; Animals; Cell Line; Cerebral Cortex/cytology; Cerebral Cortex/enzymology; Cytoplasmic Granules/enzymology; Gene Expression Regulation; Humans; Intracellular Signaling Peptides and Proteins/metabolism; Kinesin/metabolism; Mice; Neurites/enzymology; Neurons/cytology; Neurons/enzymology; Protein Binding; Protein Biosynthesis; Protein Transport; Protein-Serine-Threonine Kinases/metabolism; RNA/metabolism; RNA Transport; RNA, Messenger/genetics; RNA, Messenger/metabolism; Ribonucleoproteins/metabolism; Tissue Extracts