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Molecular and Cellular Biology, April 2003, p. 2981-2990, Vol. 23, No. 8
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.8.2981-2990.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

ASAP, a Novel Protein Complex Involved in RNA Processing and Apoptosis

Christian Schwerk,1,2 Jayendra Prasad,3 Kurt Degenhardt,1,4 Hediye Erdjument-Bromage,5 Eileen White,1,4 Paul Tempst,5 Vincent J. Kidd,6 James L. Manley,3 Jill M. Lahti,6 and Danny Reinberg1,2*

Howard Hughes Medical Institute,1 and Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School,2 Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854,4 Department of Biological Sciences, Columbia University, New York, New York 10027,3 Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021,5 Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 381056

Received 11 November 2002/ Returned for modification 30 December 2002/ Accepted 23 January 2003

Different isoforms of a protein complex termed the apoptosis- and splicing-associated protein (ASAP) were isolated from HeLa cell extract. ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein. While Acinus had previously been implicated in apoptosis and was recently identified as a component of the spliceosome, RNPS1 has been described as a general activator of RNA processing. Addition of ASAP isoforms to in vitro splicing reactions inhibits RNA processing mediated by ASF/SF2, by SC35, or by RNPS1. Additionally, microinjection of ASAP complexes into mammalian cells resulted in acceleration of cell death. Importantly, after induction of apoptosis the ASAP complex disassembles. Taken together, our results suggest an important role for the ASAP complexes in linking RNA processing and apoptosis.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854. Phone: (732) 235-4195. Fax: (732) 235-5294. E-mail: reinbedf{at}UMDNJ.edu.

Molecular and Cellular Biology, April 2003, p. 2981-2990, Vol. 23, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.8.2981-2990.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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