A serine kinase regulates intracellular localization of splicing factors in the cell cycle.
Small nuclear ribonucleoprotein particles (snRNPs) and non-snRNP splicing factors containing a serine/arginine-rich domain (SR proteins) concentrate in 'speckles' in the nucleus of interphase cells. It is believed that nuclear speckles act as storage sites for splicing factors while splicing occurs on nascent transcripts. Splicing factors redistribute in response to transcription inhibition or viral infection, and nuclear speckles break down and reform as cells progress through mitosis. We have now identified and cloned a kinase, SRPK1, which is regulated by the cell cycle and is specific for SR proteins; this kinase is related to a Caenorhabditis elegans kinase and to the fission yeast kinase Dsk1 (ref. 7). SRPK1 specifically induces the disassembly of nuclear speckles, and a high level of SRPK1 inhibits splicing in vitro. Our results indicate that SRPK1 may have a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells, and the reorganization of nuclear speckles during mitosis.
Gui
J F
JF
Division of Cellular and Molecular Medicine, University of California at San Diego 92093-0651.
Lane
W S
WS
Fu
X D
XD
D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism; D001483:Base Sequence; D002453:Cell Cycle; D003001:Cloning, Molecular; D004247:DNA; D005656:Fungal Proteins / Q000378:metabolism; D006367:HeLa Cells; D015801:Helminth Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors
D005656:Fungal Proteins; D015801:Helminth Proteins; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; D012694:Serine; D004247:DNA; D001120:Arginine; C087728:SRPK1 protein, human; D017346:Protein Serine-Threonine Kinases