Editorial MEDIATOR SPECIAL ISSUE 221 Mediator comes of age Roger D. Kornberg Update | Research Focus 222 How an enzyme answers multiple-choice questions Jennifer A. McCourt and Ronald G. Duggleby 225 Deoxyribonucleoside kinases: two enzyme families catalyze the same reaction Michael P.B. Sandrini and Jure Pis ˇkur 228 A putative nuclear function for mammalian Staufen Michael A. Kiebler, Ralf-Peter Jansen, Ralf Dahm and Paolo Macchi 231 DNA aptamers as potential anti-HIV agents Shan-Ho Chou, Ko-Hsin Chin and Andrew H-J. Wang Review MEDIATOR SPECIAL ISSUE 235 Mediator and the mechanism of transcriptional activation Roger D. Kornberg 240 The yeast Mediator complex and its regulation Stefan Bjo ¨ rklund and Claes M. Gustafsson 245 Interactions between subunits of Drosophila Mediator and activator proteins Young-Joon Kim and John T. Lis 250 The mammalian Mediator complex and its role in transcriptional regulation Ronald C. Conaway, Shigeo Sato, Chieri Tomomori-Sato, Tingting Yao and Joan W. Conaway 256 Dynamic regulation of pol II transcription by the mammalian Mediator complex Sohail Malik and Robert G. Roeder 264 Structure of eukaryotic Mediator complexes James Z. Chadick and Francisco J. Asturias TRENDS in May 2005 Vol. 30, No. 5 pp. 221 – 272 Biochemical Sciences Editor Fiona G. Hutton Assistant Editor Vicky Ashton Editorial Coordinator Joanna Pinto Illustrations The Studio Cover Design Geraldine Woods Publishing Manager O. Claire Moulton Editorial Enquiries Trends in Biochemical Sciences Elsevier, 84 Theobald’s Road, London, UK WC1X 8RR tel: +44 (0)20 7611 4400 fax: +44 (0)20 7611 4470 e-mail: tibs@elsevier.com Subscription Enquiries E-mail: ct.subs@qss-uk.com Advisory Editorial Board J. Witkowski (Editor in Chief), Cold Spring Harbor Laboratory, USA M. Bienz, MRC, Cambridge, UK S. Cockcroft, University College London, UK J. Dixon, University of California, USA T. Gibson, EMBL, Germany C-H. Heldin, Ludwig Institute for Cancer Research, Sweden M. Hentze, EMBL, Germany R. Kornberg, Stanford University, USA T. de Lange, Rockefeller University, USA A. Lamond, University of Dundee, UK G. Petsko, Brandeis University, USA T. Pollard, Yale University, USA D.W. Russell, UT Southwestern Medical Center, USA P. Schimmel, The Scripps Research Institute, USA P.H. von Hippel, University of Oregon, USA M. Yanagida, Kyoto University, Japan Forthcoming articles To celebrate 50 years of the IUBMB, the next issue of TiBS will include the following specially commissioned Editorials IUBMB: the first half century M. Osborn The discovery of split genes and RNA splicing P.A. Sharp RNA silencing D. Baulcombe The ribosome revealed P.B. Moore and T.A. Steitz Regulated protein degradation A. Varshavsky Regulation of transcription: from lambda to eukaryotes M. Ptashne Protein phosphorylation in signaling – 50 years and counting T. Pawson and J.D. Scott Cover: Synthesis of mRNA in eukaryotes is carried out by RNA polymerase II (pol II), the enzyme that provides the catalytic activity for RNA polymerization. To recognise promoter DNA and initiate transcription, pol II must associate with at least five general transcription factors that, together, assemble on a promoter to form the transcription preinitiation complex. The multiprotein Mediator complex functions as an essential regulatory component of this transcription machinery and has a crucial role in the activation and repression of eukaryotic mRNA synthesis. This special issue focuses on Mediator in a series of reviews commissioned by Roger Kornberg of the TiBS Editorial Board. (The cover image is the structural interaction of Mediator and pol II, termed the ‘holoenzyme complex’.)