Activation of pre-mRNA splicing by human RNPS1 is regulated by CK2 phosphorylation.
Human RNPS1 was originally characterized as a pre-mRNA splicing activator in vitro and was shown to regulate alternative splicing in vivo. RNPS1 was also identified as a protein component of the splicing-dependent mRNP complex, or exon-exon junction complex (EJC), and a role for RNPS1 in postsplicing processes has been proposed. Here we demonstrate that RNPS1 incorporates into active spliceosomes, enhances the formation of the ATP-dependent A complex, and promotes the generation of both intermediate and final spliced products. RNPS1 is phosphorylated in vivo and interacts with the CK2 (casein kinase II) protein kinase. Serine 53 (Ser-53) of RNPS1 was identified as the major phosphorylation site for CK2 in vitro, and the same site is also phosphorylated in vivo. The phosphorylation status of Ser-53 significantly affects splicing activation in vitro, but it does not perturb the nuclear localization of RNPS1. In vivo experiments indicated that the phosphorylation of RNPS1 at Ser-53 influences the efficiencies of both splicing and translation. We propose that RNPS1 is a splicing regulator whose activator function is controlled in part by CK2 phosphorylation.
Trembley
Janeen H
JH
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, P.O. Box 016129, Miami, FL 33101-6129, USA.
Tatsumi
Sawako
S
Sakashita
Eiji
E
Loyer
Pascal
P
Slaughter
Clive A
CA
Suzuki
Hitoshi
H
Endo
Hitoshi
H
Kidd
Vincent J
VJ
Mayeda
Akila
A
D047390:Casein Kinase II / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D005091:Exons / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing / Q000502:physiology*; D012261:Ribonucleoproteins / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism*
D012322:RNA Precursors; C084538:RNPS1 protein, human; D012261:Ribonucleoproteins; D012694:Serine; D047390:Casein Kinase II