Review RNA polymerase III transcription control elements: Themes and variations Andrea Orioli a, 1 , Chiara Pascali a, b , Aldo Pagano c , Martin Teichmann b , Giorgio Dieci a, ⁎ a Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi di Parma, Parco Area delle Scienze 23/A, 43124 Parma, Italy b Institut Européen de Chimie et Biologie/Université Bordeaux Segalen, Institut National de la Santé et de la Recherche Médicale (INSERM) U869, 33607 Pessac, France c Oncology Biology and Genetics Department (DOBiG), University of Genoa, Italy abstract article info Article history: Accepted 9 June 2011 Available online 25 June 2011 Received by A.J. van Wijnen Keywords: RNA polymerase III B box TFIIIC TFIIIB tRNA ncRNA Eukaryotic genomes are punctuated by a multitude of tiny genetic elements, that share the property of being recognized and transcribed by the RNA polymerase (Pol) III machinery to produce a variety of small, abundant non-protein-coding (nc) RNAs (tRNAs, 5S rRNA, U6 snRNA and many others). The highly selective, efficient and localized action of Pol III at its minute genomic targets is made possible by a handful of cis-acting regulatory elements, located within the transcribed region (where they are bound by the multisubunit assembly factor TFIIIC) and/or upstream of the transcription start site. Most of them participate directly or indirectly in the ultimate recruitment of TFIIIB, a key multiprotein initiation factor able to direct, once assembled, multiple transcription cycles by Pol III. But the peculiar efficiency and selectivity of Pol III transcription also depends on its ability to recognize very simple and precisely positioned termination signals. Studies in the last few years have significantly expanded the set of known Pol III-associated loci in genomes and, concomitantly, have revealed unexpected features of Pol III cis-regulatory elements in terms of variety, function, genomic location and potential contribution to transcriptome complexity. Here we review, in a historical perspective, well established and newly acquired knowledge about Pol III transcription control elements, with the aim of providing a useful reference for future studies of the Pol III system, which we anticipate will be numerous and intriguing for years to come. © 2011 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185 2. The B box, or how to recruit TFIIIC to DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 3. The A box as a fundamental core promoter element in Pol III transcription . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188 4. Upstream elements in TFIIIC-dependent Pol III transcription . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 5. Usptream elements in TFIIIC-independent Pol III transcription . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 6. Pol III termination signals: strengths and weaknesses of T-richness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190 7. Concluding remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 1. Introduction In the nucleus of all eukaryotic cells, three RNA polymerases (Pols), designated Pol I, II and III, are in charge of transcribing non- overlapping subsets of genes, being assisted in this task by complex sets of basal and regulatory transcription factors (TFs). As a result of their cumulated actions, a significant proportion of the genome is expressed to generate a highly complex, heteroge- neous transcriptome that includes protein-coding mRNAs, the well known non-protein-coding (nc) RNAs involved in protein synthesis (rRNA, tRNA) and pre-mRNA splicing (U-type snRNAs), Gene 493 (2012) 185–194 Abbreviations: Pol, RNA polymerase; TF, transcription factor; ncRNA, non-protein- coding RNA; TSS, transcription start site; SINE, short interspersed repeated DNA element; PSE, proximal sequence element; ChIP, chromatin immunoprecipitation; PIC, preinitiation complex; TBP, TATA box binding protein; DSE, distal sequence element; SBF, SPH binding factor; USE, upstream sequence element. ⁎ Corresponding author. Tel.: + 39 0521 905649; fax: + 39 0521 905151. E-mail address: giorgio.dieci@unipr.it (G. Dieci). 1 Present address: Faculty of Biology and Medicine, Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. 0378-1119/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.gene.2011.06.015 Contents lists available at ScienceDirect Gene journal homepage: www.elsevier.com/locate/gene