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Molecular and Cellular Biology, December 2007, p. 8848-8858, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.01186-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Sumoylation Modulates the Assembly and Activity of the Pre-mRNA 3' Processing Complex{triangledown} ,{dagger}

Vasupradha Vethantham, Nishta Rao, and James L. Manley*

Department of Biological Sciences, Columbia University, New York, New York 10027

Received 3 July 2007/ Returned for modification 9 August 2007/ Accepted 21 September 2007

Eukaryotic pre-mRNA 3'-end formation is catalyzed by a complex set of factors that must be intricately regulated. In this study, we have discovered a novel role for the small ubiquitin-like modifier SUMO in the regulation of mammalian 3'-end processing. We identified symplekin, a factor involved in complex assembly, and CPSF-73, an endonuclease, as SUMO modification substrates. The major sites of sumoylation in symplekin and CPSF-73 were determined and found to be highly conserved across species. A sumoylation-deficient mutant was defective in rescuing cell viability in symplekin small interfering RNA (siRNA)-treated cells, supporting the importance of this modification in symplekin function. We also analyzed the involvement of sumoylation in 3'-end processing by altering the sumoylation status of nuclear extracts. This was done by the addition of a SUMO protease, which we show interacts with both symplekin and CPSF-73, or by siRNA-mediated depletion of ubc9, the SUMO E2-conjugating enzyme. Both treatments resulted in a marked inhibition of processing. The assembly of a functional polyadenylation complex was also impaired by the SUMO protease. Our identification of two key polyadenylation factors as SUMO targets and of the role of SUMO in enhancing the assembly and activity of the 3'-end-processing complex together reveal an important function for SUMO in the processing of mRNA precursors.

* Corresponding author. Mailing address: Department of Biological Sciences, 1117 Fairchild Center, Columbia University, New York, NY 10027. Phone: (212) 854-4647. Fax: (212) 865-8246. E-mail: jlm2{at}columbia.edu

{triangledown} Published ahead of print on 8 October 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, December 2007, p. 8848-8858, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.01186-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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