Mechanisms of mRNA and sn(o)RNA Synthesis in Saccharomyces cerevisiae
Bernhard Dichtl
Dr. Bernhard Dichtl
SNF-Förderungsprofessor
Institut für Molekularbiologie
Universität Zürich
Winterthurerstrasse 190
8057 Zürich
Schweiz
+41 44 63 53160 (tel)
+41 44 63 56811 (fax)
bernhard.dichtl(at)molbio.unizh.ch
Group members
Research summary
The synthesis of functional mRNA templates for protein expression and of a large number of small and stable sn(o)RNAs requires transcription by RNA polymerase II and extensive RNA processing. Recent advances in the understanding of both transcription and of RNA processing revealed intimate connections between these processes in vivo. Elongating RNA polymerase II not only integrates the chromatin template and the RNA transcript, but also a large number of associated protein factors including RNA processing enzymes. Remarkably, processing factors impact heavily on transcription and vice versa, transcription factors can profoundly influence processing. To increase the understanding of transcription and of RNA processing it is necessary to analyze the production of mature RNAs with the consideration that these processes are highly interdependent in vivo. We will functionally analyze RNAP II elongation complexes with the aim to better understand the mechanisms and regulation of mRNA and sn(o)RNA synthesis. Major goals of our work are: 1) to identify novel factors that associate with RNAP II during transcription and to understand how they function in transcription and/or RNA processing; 2) to elucidate the molecular mechanisms that act during termination of processive RNA synthesis by RNA polymerase II; 3) to understand how 3’ end formation factors influence elongating RNA polymerase II during different steps of the transcription cycle.
We use the yeast Saccharomyces cerevisiae as a model system for analyses since it can be manipulated with ease. The genetic, biochemical and proteomic methodologies and tools available for yeast are strongly superior to other eukaryotic model organisms currently studied. Importantly, the insights gained from the yeast system most certainly will provide important knowledge for RNA synthesis also in higher eukaryotes (including humans) since many of the basic biochemical mechanisms and the factors involved are conserved in evolution.
Publications
Holbein S, Wengi A, Decourty L, Freimoser FM, Jacquier A and Dichtl B (2009) "Cordycepin interferes with 3' end formation in yeast independently of its potential to terminate RNA chain elongation." RNA Abstract
Garas M, Dichtl B and Keller W (2008) "The role of the putative 3' end processing endonuclease Ysh1p in mRNA and snoRNA synthesis." Rna 14(12): 2671-2684. Abstract
Dichtl B (2008) "Transcriptional ShortCUTs." Mol Cell 31(5): 617-618. Abstract
Holbein S, Freimoser FM, Werner TP, Wengi A and Dichtl B (2008) "Cordycepin-hypersensitive growth links elevated polyphosphate levels to inhibition of poly(A) polymerase in Saccharomyces cerevisiae." Nucleic Acids Res 36(2): 353-363. Abstract
Dehe PM, Dichtl B, Schaft D, Roguev A, Pamblanco M, Lebrun R, Rodriguez-Gil A, Mkandawire M, Landsberg K, Shevchenko A, Shevchenko A, Rosaleny LE, Tordera V, Chavez S, Stewart AF and Geli V (2006) "Protein interactions within the Set1 complex and their roles in the regulation of histone 3 lysine 4 methylation." J Biol Chem 281(46): 35404-35412. Abstract
Morlando M, Ballarino M, Greco P, Caffarelli E, Dichtl B and Bozzoni I (2004) "Coupling between snoRNP assembly and 3' processing controls box C/D snoRNA biosynthesis in yeast." Embo J 23(12):2392-2401 Abstract
Dichtl B, Aasland R and Keller W (2004) "Functions for S. cerevisiae Swd2p in 3' end formation of specific mRNAs and snoRNAs and global histone 3 lysine 4 methylation." Rna 10(6):965-977 Abstract
Kyburz A, Sadowski M, Dichtl B and Keller W (2003) "The role of the yeast cleavage and polyadenylation factor subunit Ydh1p/Cft2p in pre-mRNA 3'-end formation." Nucleic Acids Res 31(14):3936-3945 Abstract
Sadowski M, Dichtl B, Hubner W and Keller W (2003) "Independent functions of yeast Pcf11p in pre-mRNA 3' end processing and in transcription termination." Embo J 22(9):2167-2177 Abstract
Dichtl B, Blank D, Ohnacker M, Friedlein A, Roeder D, Langen H and Keller W (2002) "A role for SSU72 in balancing RNA polymerase II transcription elongation and termination." Mol Cell 10(5):1139-1150 Abstract
Morlando M, Greco P, Dichtl B, Fatica A, Keller W and Bozzoni I (2002) "Functional analysis of yeast snoRNA and snRNA 3'-end formation mediated by uncoupling of cleavage and polyadenylation." Mol Cell Biol 22(5):1379-1389 Abstract
Dichtl B, Blank D, Sadowski M, Hubner W, Weiser S and Keller W (2002) "Yhh1p/Cft1p directly links poly(A) site recognition and RNA polymerase II transcription termination." Embo J 21(15):4125-4135 Abstract
Dichtl B and Keller W (2001) "Recognition of polyadenylation sites in yeast pre-mRNAs by cleavage and polyadenylation factor." Embo J 20(12):3197-3209 Abstract
Kufel J, Dichtl B and Tollervey D (1999) "Yeast Rnt1p is required for cleavage of the pre-ribosomal RNA in the 3' ETS but not the 5' ETS." Rna 5(7):909-917 Abstract
Dichtl B, Stevens A and Tollervey D (1997) "Lithium toxicity in yeast is due to the inhibition of RNA processing enzymes." Embo J 16(23):7184-7195 Abstract
Dichtl B and Tollervey D (1997) "Pop3p is essential for the activity of the RNase MRP and RNase P ribonucleoproteins in vivo." Embo J 16(2):417-429 Abstract
Pan T, Dichtl B and Uhlenbeck OC (1994) "Properties of an in vitro selected Pb2+ cleavage motif." Biochemistry 33(32):9561-9565 Abstract
Dichtl B, Pan T, DiRenzo AB and Uhlenbeck OC (1993) "Replacement of RNA hairpins by in vitro selected tetranucleotides." Nucleic Acids Res 21(3):531-535 Abstract
