DYRK1A accumulates in splicing speckles through a novel targeting signal and induces speckle disassembly.
The protein kinase DYRK1A is distributed throughout the nucleoplasm, accumulating in speckle-like regions. We have found that this punctuated nuclear distribution is determined by the contribution of several elements. Although the nuclear import is mediated by two distinct nuclear localization signals, one at the N-terminus and the other located in the linker region, between subdomains X and XI of the catalytic domain, the accumulation in speckles that are SC35 positive depends on a sequence motif that is located C-terminal to the kinase domain and comprises a histidine tail. A similar sequence is also responsible for the targeting of cyclin T1. Therefore the histidine-rich region represents a novel splicing speckle targeting signal. Moreover, overexpression of DYRK1A induces speckle disassembly. Such disassembly is DYRK1A activity specific, since the overexpression of a DYRK1A kinase inactive mutant, the paralogous DYRK1B or a chimeric protein DYRK1B that has been directed to the speckles via the DYRK1A targeting signal, leaves the SC35 speckle pattern untouched. Thus DYRK1A protein kinase may play a role in regulating the biogenesis of the splicing speckle compartment.
Alvarez
Monica
M
Program in Genes and Disease, Centre de Regulació Genòmica-CRG, Passeig Marítim 37-49, 08003-Barcelona, Spain.
Estivill
Xavier
X
de la Luna
Susana
S
D000818:Animals; D019556:COS Cells; D020134:Catalytic Domain / Q000235:genetics; D002522:Chlorocebus aethiops; D056906:Cyclin T; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012326:RNA Splicing; D012261:Ribonucleoproteins; D000068103:Serine-Arginine Splicing Factors; D017381:Spliceosomes / Q000378:metabolism*; D000097603:Dyrk Kinases
D056906:Cyclin T; D016213:Cyclins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D012261:Ribonucleoproteins; D000068103:Serine-Arginine Splicing Factors; D000097603:Dyrk Kinases; C503684:CCNT1 protein, human; C073288:SRSF2 protein, human