Specific phosphorylation of SR proteins by mammalian DNA topoisomerase I

SEVERAL metazoan splicing factors are characterized by ribo-nucleoprotein (RNP) consensus sequences and arginine–serine repeats (RS domain) 1–8 which are essential for their function in splicing 5,9,10 . These include members of the SR-protein family (SC35, SF2/ASF), the U1 small nuclear (sn)RNP pro...

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Bibliographic Details
Published in:Nature (London) 1996-05, Vol.381 (6577), p.80-82
Main Authors: Rossi, Ferdinand, Labourier, Emmanuel, Forné, Thierry, Divita, Gilles, Derancourt, Jean, Riou, Jean François, Antoine, Etienne, Cathala, Guy, Brunel, Claude, Tazi, Jamal
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
ATP
Biological and medical sciences
Camptothecin - analogs & derivatives
Camptothecin - pharmacology
Cell Line
Deoxyribonucleic acid
DNA
DNA Topoisomerases, Type I - genetics
DNA Topoisomerases, Type I - metabolism
Fundamental and applied biological sciences. Psychology
HeLa Cells
Humanities and Social Sciences
Humans
letter
Mammals
Metazoa
Molecular and cellular biology
Molecular genetics
multidisciplinary
Nuclear Proteins - metabolism
Phosphorylation - drug effects
Protein Kinases - metabolism
Proteins
Recombinant Proteins - metabolism
RNA-Binding Proteins
Science
Science (multidisciplinary)
Serine-Arginine Splicing Factors
Topotecan
Transcription. Transcription factor. Splicing. Rna processing
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Summary:SEVERAL metazoan splicing factors are characterized by ribo-nucleoprotein (RNP) consensus sequences and arginine–serine repeats (RS domain) 1–8 which are essential for their function in splicing 5,9,10 . These include members of the SR-protein family (SC35, SF2/ASF), the U1 small nuclear (sn)RNP protein (U1-70K) and the U2 snRNP auxiliary factor (U2AF). SR proteins are phosphorylated in vivo 11 and the phosphorylation state of U1-70K's RS domain influences its splicing activity 12 . Here we report the purification of a protein kinase that is specific for SR proteins and show that it is DNA topoisomerase I. This enzyme lacks a canonical ATP-binding motif but binds ATP with a dissociation constant of 50 nM. Camptothecin and derivatives, known to be specific inhibitors of DNA topoisomerase I, strongly inhibit the kinase activity in the presence of DNA and affect the phosphorylation state of SR proteins. Thus, DNA topoisomerase I may well be one of the SR protein kinases operating in vivo .
ISSN:0028-0836
1476-4687
DOI:10.1038/381080a0