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Vol. 17, Issue 10, 4228-4236, October 2006

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The mRNA Export Factor Sus1 Is Involved in Spt/Ada/Gcn5 Acetyltransferase-mediated H2B Deubiquitinylation through Its Interaction with Ubp8 and Sgf11

Alwin Köhler^*,,, Pau Pascual-García^,, Ana Llopis, Meritxell Zapater^||, Francesc Posas^||, Ed Hurt^*, and Susana Rodríguez-Navarro

*Biochemie-Zentrum der Universität Heidelberg, INF328, D-69120, Heidelberg, Germany; University Children's Hospital Heidelberg, INF150, D-69120, Heidelberg, Germany; Centro de Investigación Príncipe Felipe, E-46013, Valencia, Spain; and ^||Cell Signaling Unit, Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, E-08003, Barcelona, Spain

Submitted February 3, 2006; Revised June 20, 2006; Accepted July 11, 2006
Monitoring Editor: Susan Wente

Sus1 acts in nuclear mRNA export via its association with the nuclear pore-associated Sac3–Thp1–Cdc31 complex. In addition, Sus1 plays a role in transcription through its interaction with the Spt/Ada/Gcn5 acetyltransferase (SAGA) complex. Here, we have analyzed function and interaction of Sus1 within the SAGA complex. We demonstrate that Sus1 is involved in the SAGA-dependent histone H2B deubiquitinylation and maintenance of normal H3 methylation levels. By deletion analyses, we show that binding of Sus1 to SAGA depends on the deubiquitinylating enzyme Ubp8 and Sgf11. Moreover, a stable subcomplex between Sus1, Sgf11, and Ubp8 could be dissociated from SAGA under high salt conditions. In vivo recruitment of Sus1 to the activated GAL1 promoter depends on Ubp8 and vice versa. In addition, histones coenrich during SAGA purification in a Sus1–Sgf11–Ubp8-dependent way. Interestingly, sgf11 deletion enhances the mRNA export defect observed in sus1 cells. Thus, the Sus1–Sgf11–Ubp8 module could work at the junction between SAGA-dependent transcription and nuclear mRNA export.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-02-0098) on July 19, 2006.

These authors contributed equally to this work.

Address correspondence to: Susana Rodríguez-Navarro (srodriguez{at}cipf.es)

Abbreviations used: NPC, nuclear pore complex; SAGA, Spt/Ada/Gcn5 acetyltransferase.

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