The splicing of mRNA is dependent on serine-arginine (SR) proteins that are mobilized from membrane-free, nuclear speckles to the nucleoplasm by the Cdc2-like kinases (CLKs). This movement is critical for SR protein-dependent assembly of the macromolecular spliceosome. Although CLK1 facilitates such trafficking through the phosphorylation of serine-proline dipeptides in the prototype SR protein SRSF1, an unrelated enzyme known as SR protein kinase 1 (SRPK1) performs the same function but does not efficiently modify these dipeptides in SRSF1. We now show that the ability of SRPK1 to mobilize SRSF1 from speckles to the nucleoplasm is dependent on active CLK1. Diffusion from speckles is promoted by the formation of an SRPK1–CLK1 complex that facilitates dissociation of SRSF1 from CLK1 and enhances the phosphorylation of several serine-proline dipeptides in this SR protein. Down-regulation of either kinase blocks EGF-stimulated mobilization of nuclear SRSF1. These findings establish a signaling pathway that connects SRPKs to SR protein activation through the associated CLK family of kinases.
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Cover Image
Cover Image
SR proteins guide the assembly of the macromolecular spliceosome for the splicing of precursor mRNA transcripts. In this issue of Biochemical Journal, Aubol et al. demonstrate that a complex of two protein kinases- SRPK1 and CLK1- can be induced in the nucleus to promote release of the SR protein SRSF1 from storage speckles, a critical step for splicing activation. The image shows the import of SRPK1 from the cytoplasm to the nucleus and the reduction of storage speckles upon the treatment of HeLa cells with the growth factor EGF.
Mobilization of a splicing factor through a nuclear kinase–kinase complex
Brandon E. Aubol, Malik M. Keshwani, Laurent Fattet, Joseph A. Adams; Mobilization of a splicing factor through a nuclear kinase–kinase complex. Biochem J 14 February 2018; 475 (3): 677–690. doi: https://doi.org/10.1042/BCJ20170672
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