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.
Cambray
Serafí
S
Departament de Ciències Mèdiques Bàsiques, IRBLLEIDA, Universitat de Lleida, Lleida, Catalonia, Spain.
Pedraza
Neus
N
Rafel
Marta
M
Garí
Eloi
E
Aldea
Martí
M
Gallego
Carme
C
D020413:3' Untranslated Regions / Q000378:metabolism; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology; D003594:Cytoplasmic Granules / Q000201:enzymology*; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism; D051379:Mice; D016501:Neurites / Q000201:enzymology; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D011485:Protein Binding; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D012313:RNA / Q000378:metabolism*; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D014020:Tissue Extracts
D020413:3' Untranslated Regions; D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; C490202:Kif3a protein, mouse; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D014020:Tissue Extracts; D012313:RNA; D017346:Protein Serine-Threonine Kinases; C530659:Uhmk1 protein, mouse; D016547:Kinesins