A SERINE KINASE REGULATES INTRACELLULAR-LOCALIZATION OF SPLICING FACTORS IN THE CELL CYCLE

Small nuclear ribonucleoprotein particles (snRNPs) and non-snRNP splic ing factors containing a serine/arginine-rich domain (SR proteins) con centrate in 'speckles' in the nucleus of interphase cells(1). It is be lieved that nuclear speckles act as storage sites for splicing factors while splicing occurs on nascent transcripts(2). Splicing factors red istribute in response to transcription inhibition(3,4) or viral infect ion(5), and nuclear speckles break down and reform as cells progress t hrough mitosis(6). 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 f ission yeast kinase Dsk1 (ref. 7). SRPK1 specifically induces the disa ssembly of nuclear speckles, and a high level of SRPK1 inhibits splici ng in vitro. Our results indicate that SRPK1 mag have a central role i n the regulatory network for splicing, controlling the intranuclear di stribution of splicing factors in interphase cells, and the reorganiza tion of nuclear speckles during mitosis.