SR (serine/arginine rich) protein kinase SRPK1 / peptide complex
Homo sapiens (human)
Eukaryotic mRNA is not always the complement of template DNA but is the edited product in which the untranslated regions, introns, are deleted. This RNA editing is called "RNA splicing". RNA splicing is accomplished by the enzymatic complex composed of various proteins and RNAs. One of the components of the complex is SR (serine(S)/arginine(R)-rich) protein. SR protein has RNA recognition motif (RRM) and RS domain. RS domain contains more than one arginine-serine (RS) repeat and this serine residue is the phosphorylation target of serine kinases. Phosphorylation of SR protein changes the intracellular localization of SR protein and regulates the cellular function. ASF/SF2 is an SR protein. In the cytosol, Only N-terminal part of RS domain in ASF/SF2 is phosphorylated by SR protein kinase (SRPK). C-terminal part of RS domain remains unphosphorylated in this state. This N-teminal phosphorylation of RS domain induces the translocation of ASF/SF2 from cytosol to nuclear speckle where the components needed for RNA splicing are concentrated. In the nuclear speckle, Clk/Sty, another kinase for ASF/SF2 exists. Clk/Sty phosphorylates C-terminal part of RS domain. This overphosphorylation of RS domain releases ASF/SF2 from nuclear speckle. The C-terminal part of RS domain resides next to the N-terminal domain of RS domain. Nevertheless, the phosphorylation sites of RS domain are strictly regulated. But the mechanism has not been known.
Protein Data Bank (PDB)
author: Daisuke Ino