Document Detail

Phosphorylation of human PRP28 by SRPK2 is required for integration of the U4/U6-U5 tri-snRNP into the spliceosome.
MedLine Citation:
PMID:  18425142     Owner:  NLM     Status:  MEDLINE    
Several protein kinases, including SRPK1 and SRPK2, have been implicated in spliceosome assembly and catalytic activation. However, little is known about their targets. Here we show that SRPK1 is predominantly associated with U1 small nuclear ribonucleoprotein (snRNP), whereas SRPK2 associates with the U4/U6-U5 tri-snRNP. RNAi-mediated depletion in HeLa cells showed that SRPK2 is essential for cell viability, and it is required for spliceosomal B complex formation. SRPK2 knock down results in hypophosphorylation of the arginine-serine (RS) domain-containing human PRP28 protein (PRP28, also known as DDX23), and destabilizes PRP28 association with the tri-snRNP. Immunodepletion of PRP28 from HeLa cell nuclear extract and complementation studies revealed that PRP28 phosphorylation is required for its stable association with the tri-snRNP and for tri-snRNP integration into the B complex. Our results demonstrate a role for SRPK2 in splicing and reveal a previously unknown function for PRP28 in spliceosome assembly.
Rebecca Mathew; Klaus Hartmuth; Sina Möhlmann; Henning Urlaub; Ralf Ficner; Reinhard Lührmann
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-20
Journal Detail:
Title:  Nature structural & molecular biology     Volume:  15     ISSN:  1545-9985     ISO Abbreviation:  Nat. Struct. Mol. Biol.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-07     Completed Date:  2008-05-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101186374     Medline TA:  Nat Struct Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  435-43     Citation Subset:  IM    
Department of Cellular Biochemistry MPI for Biophysical Chemistry, Am Fassberg 11, D-37077 Göttingen, Germany.
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MeSH Terms
DEAD-box RNA Helicases / metabolism*
Hela Cells
Protein-Serine-Threonine Kinases / genetics,  metabolism*
RNA Interference
RNA, Small Interfering / metabolism
Ribonucleoprotein, U1 Small Nuclear / metabolism
Ribonucleoprotein, U4-U6 Small Nuclear / metabolism*
Spliceosomes / metabolism
Reg. No./Substance:
0/RNA, Small Interfering; 0/Ribonucleoprotein, U1 Small Nuclear; 0/Ribonucleoprotein, U4-U6 Small Nuclear; EC 2.7.1.-/SRPK1 protein, human; EC Kinases; EC protein, human; EC 2.7.7.-/DDX23 protein, human; EC 3.6.1.-/DEAD-box RNA Helicases
Comment In:
Nat Struct Mol Biol. 2008 May;15(5):426-8   [PMID:  18461042 ]

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