CycliX

Nouria Hernandez

	Contact Nouria Hernandez Center for Integrative Genomics Faculty of Biology and Medicine University of Lausanne Génopode Building Dorigny Campus 1015 Lausanne Switzerland Phone: +41 21 692 3921 Email: nouria.hernandez@unil.ch
Nouria Hernandez performed her thesis research on mRNA splicing with Dr. Walter Keller at the University of Heidelberg in Germany and received her PhD in 1983. She did her postdoctoral studies with Dr. Alan M. Weiner at Yale University in New Haven, Connecticut, USA, working on 3' end formation of the U1 small nuclear RNA. She then joined Cold Spring Harbor Laboratory at Cold Spring Harbor, New York, in 1986 as an Assistant Professor. She became a Cold Spring Harbor Laboratory Professor in 1993 and joined the Howard Hughes Medical Institute as an Associate Investigator in 1994. She became a full Howard Hughes Medical Institute Investigator in 1999. In 2005, she joined the faculty of the UNIL as a Professor and as the Director of the Center for Integrative Genomics (CIG).

Current research The task of transcribing mammalian genomes is shared among three main RNA polymerases known as RNA polymerases (pol) I, II, and III. In human cells, a single polypeptide fourth polymerase (spRNAP-IV), encoded by an alternatively spliced mRNA derived from the nuclear gene for mitochondrial RNA pol, has been described. Pol I is responsible for the transcription of only one type of transcription unit, the 45S transcription unit, which is highly repeated in the human genome and gives rise to the 28S, 18S, and 5.8S ribosomal RNAs. Pol II transcribes the mRNA genes encoding proteins as well as most small nuclear RNA (snRNA) and microRNA genes. Thus, in contrast to pol I, pol II recognizes a large variety of promoter structures, reflecting the intricate regulation of mRNA genes in processes such as cell growth, cell proliferation, cell differentiation, or cell responses to various stresses. spRNAP-IV is thought to transcribe a few hundred mRNA-encoding genes. As for pol-III, it transcribes a collection of short genes encoding RNAs that are essential for cellular metabolism as well as some regulatory RNAs such as microRNAs. We are interested in several questions pertaining to mechanisms of transcription regulation of certain genes that give rise RNAs that do not code for proteins, so-called non-coding RNAs (ncRNAs). In particular we are interested in the mechanisms that govern transcription of pol III genes, which according to current knowledge all give rise to ncRNAs, as well as transcription of pol II snRNA genes. Both classes of genes are relatively understudied when compared to classical pol II mRNA-encoding genes. Current work is focused on understanding the interplay between transcription factors involved in both pol II and pol III transcription of snRNA genes, on understanding the mechanisms of action of the pol III repressor Maf1, on determining how broadly the known pol III transcription machinery is used on a genome-wide scale in human cells, and on determining the human pol III transcriptome. For more information, see . Keywords RNA polymerase III, non-coding RNAs, Bdp1, Brf1, Brf2, SNAPc, gene regulation networks

Role within the CycliX Consortium

We will use chromatin immunoprecipitations with antibodies directed against members of the pol III transcription machinery including pol III itself, as well as with antibodies directed against certain transcription factors such as SNAPc, which are used for transcription of both pol II and III genes producing ncRNAs, to establish genome-wide occupancy maps for these factors at different stages of the circadian-, cell division-, and nutrition cycle. These maps will reveal which of these ncRNA genes vary, in terms of their transcription status, during one or more of the three cycles. We will then search for active enhancers of repressors controlling these genes. We will be particularly interested in pol III and pol II snRNA genes varying during more than one cycle (cyclic node genes), as some of these may be involved in connecting cycles. These maps will serve for the identification of common regulatory elements and transcription factors acting at cyclic nodes, followed by experimental tests of the function of such transcription factors in connecting cycles.

Relevant publications:

Schramm, L., and Hernandez, N. (2002) Recruitment of RNA polymerase III to its target promoters. Genes & Dev. 16, 2593-2620.

Michels, A.A., and Hernandez, N. (2006). Does Pol I talk to Pol II? Coordination of RNA polymerases in ribosome biogenesis. Genes & Dev. 20, 1982-1985.

Reina, J.H., Azzouz, T.N., and Hernandez, N. (2006). Maf1, a new player in the regulation of human RNA polymerase III transcription. PLoS ONE 1, e134.

Denissov, S., van Driel, M., Voit, R., Hekkelman, M., Hulsen, T., Hernandez, N., Grummt, I., Wehrens, R., and Stunnenberg, H. (2007). Identification of novel functional TBP-binding sites and general factor repertoires. EMBO J. 26, 944-954.

Canella, D., Praz, V., Reina, J. H., Cousin, P., and Hernandez, N. Defining the RNA polymerase III transcriptome: genome-wide localization of the RNA polymerase III transcription machinery in human cells. Submitted.