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Swiss Rna Workshop Presentation overview 2 Talks: Last First Group Page Nr. Tanackovic Goranka Rivolta 5 Chabot Benoit Chabot 6 Meyer Kathrin Schümperli 7 Clèry Antoine Allain 8 Chari Ashwin Fischer 9 Beyrouthy Nissrine Stutz 10 Luke Brian Lingner 11 Gerber André P. Gerber 12 Hentze Matthias W. Hentze 13 Grosshans Helge Grosshans 14 Hausser Jean Zavolan 15 Chandrasekar Vijay Dreyer 16 Nicholson Pamela Mühlemann 17 San Paolo Salvatore Keller 18 Aeby Eric Schneider 19 Ochsenreiter Torsten Ochsenreiter 20 SWISS RNA WORKSHOP Posters: January 30, 2009, Nr. Last First Group Page Nr. 9:15-18:20h 1 Lenzken Silvia C Barabino 21 2 Vivarelli Silvia Barabino 22 3 Graef Christine Baumann 23 4 Kowalska Elzbieta Brown 24 5 Scheckel Claudia Ciosk 25 6 Wright Jane Ciosk 26 7 Halbach Andre Dichtl 27 Universität Bern, UniS, Schanzeneckstr. 1, Hörsaal A003 8 Scola Simonetta Dichtl 28 9 Kanitz Alexander Gerber 29 Organizers: Angela Krämer, Oliver Mühlemann 10 Schenk Luca Gerber 30 and Daniel Schümperli 11 Scherrer Tanja Gerber 31 12 Hertel Klemens Hertel 32 13 Karow Anne R. Klostermeier 33 14 Panza Andrea B. Lingner 34 15 Mendes Camila T. Lottaz 35 16 Sánchez Freire Verónica Monastyrskaya 36 17 Stalder Lukas Mühlemann 37 18 Pauli Sandra Nagamine 38 19 Leidel Sebastian Peter 39 20 Ramundo Silvia Rochaix 40 21 Ruepp Marc-David Schümperli 41 22 Dieppois Guennaëlle Stutz 42 23 Tutucci Evelina Stutz 43 Sponsored by: 24 Meili David Thoeny 44 25 Swetloff Adam Patrick Vassalli 45 26 Bandi Nora Vassella 46 Morning program 3 Afternoon program 4 Opening remarks (9:15) Lunch and poster session (12:40-14:10) Angela Krämer, Department of Cell Biology, University of Geneva Daniel Schümperli, Institute of Cell Biology, University of Bern MicroRNAs and RNA binding proteins - Splicing and disease (9:25-10:40) control of translation and mRNA stability (14:10-16:05) Analysis of pre-mRNA splicing in cell lines derived from patients with retinitis Stress-dependent coordination of transcriptome and translatome in yeast pigmentosa and dominant mutations in pre-mRNA splicing factor genes PRPF31, André P. Gerber PRPF8 and PRPF3 Institute of Pharmaceutical Sciences, ETH Zürich Goranka Tanackovic (C. Rivolta) Department of Medical Genetics, University of Lausanne, Switzerland Translational control by miRNAs and RNA-binding proteins Matthias W. Hentze SR, hnRNP, PKC and EJC: Converging complexity to control the splicing of the European Molecular Biology Laboratory, Heidelberg, Germany apoptotic regulator Bcl-x Benoit Chabot Function and regulation of the let-7 microRNA Département de microbiologie et d’infectiologie, Université de Sherbrooke, Québec, Canada Helge Grosshans Friedrich Miescher Institute for Biomedical Research, Basel. In vivo splicing modulation rescues a severe mouse model for Spinal Muscular Atrophy To be or not to be a miRNA target site Kathrin Meyer (D. Schümperli) Jean Hausser (M. Zavolan) Institute of Cell Biology, University of Bern University of Basel, Biozentrum. 4056 Basel, Switzerland MicroRNA feed back loop in cocaine induced synaptic plasticity and addiction Vijay Chandrasekar (J.-L. Dreyer) Institute of Biochemistry, University of Fribourg Coffee break and setting up of posters (10:40-11:20) Structures of RNPs (11:20-12:00) Coffee break and poster session (16:05-17:00) NMR structure of the tra21 splicing factor in complex with RNA revealed an unexpected extensive interaction with the C-terminal extremity of the RRM Quality control (17:00-17:40) Antoine Cléry (F. Allain) Institute for Molecular Biology and Biophysics, ETH Zürich SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells Pamela Nicholson (O. Mühlemann) An assembly chaperone collaborates with the SMN-complex to generate spliceosomal Institute of Cell Biology, University of Bern, Switzerland snRNPs Ashwin Chari (U. Fischer) Genome-wide analysis of the non-canonical poly(A) polymerases Trf4p and Trf5p: Department of Biochemistry, University of Würzburg, Germany more than RNA quality control Salvatore San Paolo (W. Keller) Biozentrum, Cell Biology, University of Basel, Switzerland Nuclear regulation (12:00-12:40) Trans-acting antisense RNAs mediate transcriptional gene cosuppression in Alternative coding (17:40-18:20) S. cerevisiae Nissrine Beyrouthy (F. Stutz) In vivo analysis of selenocysteine synthesis shows a single pathway in eukaryotes Department of Cell Biology, University of Geneva Eric Aeby (A.Schneider) Department of Chemistry and Biochemistry, University of Bern Yeast telomere repeat containing RNA (TERRA) and telomere length regulation Brian Luke (J. Lingner) Alternative RNA editing creates novel proteins in trypanosome mitochondria ISREC, Epalinges Torsten Ochsenreiter Institute of Cell Biology, University of Bern Abstracts of oral presentations (in order of the program) 5 Abstracts of oral presentations (in order of the program) 6 Analysis of pre-mRNA splicing in cell lines derived from SR, hnRNP, PKC and EJC: Converging complexity to patients with retinitis pigmentosa and dominant mutations control the splicing of the apoptotic regulator Bcl-x in pre-mRNA splicing factor genes PRPF31, PRPF8 and Benoit Chabot PRPF3 Département de microbiologie et d’infectiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada Goranka Tanackovic1, Adriana Ransijn1, Jacques S. Beckmann1, Eliot L. Berson2 1 and Carlo Rivolta The Bcl-x pre-mRNA is alternatively spliced to produce the anti-apoptotic Bcl-xL and the 1Department of Medical Genetics, University of Lausanne, Switzerland 2 pro-apoptotic Bcl-xS isoforms. We have identified a variety of exon elements that control the The Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard use of the 5’ splice sites of Bcl-x. One element is bound by SRp30c to activate the xL site Medical School, Boston, USA while others are bound by hnRNP F/H et hnRNP K to activate and repress the xS site. Another element strongly represses the xS site and requires protein kinase C activity. This Pre-mRNA splicing is a process in which introns are removed from pre-mRNA and exons sequence element appears to represent a converging platform for many signaling routes that are joined together to produce mRNA. It is catalyzed by complex molecular machinery termed monitor stresses and translation efficacy. Further, our screening platform has identified two spliceosome, composed of five snRNPs and numerous non-snRNP proteins. In addition to components of the exon junction complex (EJC) involved in the control of Bcl-x splicing. providing mature mRNA molecules to the cell, it contributes to protein diversity in higher These proteins also coregulate the alternative splicing of other apoptotic genes. Because EJC eukaryotes through the process of alternative splicing, which allows the production of different components are important for the decay of aberrant mRNAs with premature termination mRNA molecules, and thus proteins, from a single pre-mRNA. Dysfunctions of splicing often lead to diseases and one of these is Retinitis pigmentosa (RP). codons, a reduction in the level of these proteins may trigger apoptosis by encouraging the RP is the most common form of hereditary retinal degeneration, affecting 1/4000 individual production of pro-apoptotic splice forms. worldwide. Clinically, it is characterized by progressive loss of vision and can lead to complete blindness because of the death of photoreceptors, the light-sensing cells of the retina. Genetically, this is a very heterogeneous disorder, caused by mutations in roughly 50 different genes. Most of these are retina-specific or have a well-defined role in the physiology of photoreceptors; others are expressed in many tissues or are ubiquitous and yet cause a phenotype that is retina-specific. Among the ubiquitous genes are PAP-1 (RP9), PRPF31 (RP11), PRPF8 (RP13), and PRPF3 (RP18), all encoding pre-mRNA splicing factors that are very conserved and essential for viability. All these genes encode proteins that are part of U4/U6-U5 tri-snRNP particle that represents, in addition to U1 and U2 snRNPs, a key component of the spliceosome. The aim of our work is to understand why mutations in the ubiquitously expressed genes: PRPF31, PRPF8 and PRPF3 affect only one tissue – the retina. Moreover, from the mechanistic point of view, the nature of the mutations in these RP genes is different. Most of the PRPF31 mutations lead to premature stop codons and degradation of the mutant mRNA by nonsense- mediated decay, therefore in heterozygous patients PRPF31 is expressed at lower amounts and only from the wild-type allele, probably causing the disease through an haploinsufficiency- dependent mechanism. The RP-causing mutations in PRPF8 and PRPF3 genes are missense mutations or indels leading to premature stops in the last exon and may therefore potentially act as dominant-negative alleles. We are interested to know how decreased levels of PRPF31 protein or mutations in PRPF3 and PRPF8 affect pre-mRNA splicing. We have studied in vitro spliceosome formation, as well as in vitro and in vivo splicing using lymphoblastoid cells derived from RP patients carrying various mutations in the above- mentioned PRPF genes. Our results show that mutations in these genes slow down kinetics of spliceosome assembly; however they do not block splicing of the pre-mRNA tested. This could indirectly suggest that tissue-specific alternative splicing patterns could be affected in the case of RP11, RP13 and RP18 mutations and we are currently testing this hypothesis. Abstracts of oral presentations
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