Instytut Biochemii i Biofizyki Polskiej Akademii Nauk  Wydział Biologii Uniwersytetu Warszawskiego
Eucaryotic RNA decay and processing

Eucaryotic RNA decay and processing

In recent years several important discoveries, such as RNA interference and its influence on chromatin structure, various RNA surveillance pathways etc., have focused the researchers’ attention on posttranscriptional life of RNA. The major interests of the laboratory concern the analysis multi-protein complexes involved in RNA metabolism. We combine biochemical and functional studies with structural biology approaches in order to achieve deep insight into the analyzed complexes. Moreover, we employ high throughput technologies like deep sequencing to get a genome-wide view of the functions of the analyzed proteins and complexes.
Our model organisms are yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe, various cell lines, mice and the worm Caenorhabditis elegans
The major projects regarding this topic are:

  • Functional and structural studies of the major eukaryotic ribounclease, the exosome complex, and its cofactors
  • Role of the exosome catalytic subunit DIS3 in the pathogenesis of multiple myeloma
  • Functional and structural studies of mRNA processing and export factors
  • Identification of novel enzymes involved in RNA decay and modifications
  • Mitochondrial RNA decay

People involved:

Recent: Łukasz Borowski, Aleksander Chlebowski, Mariusz Czarnocki-Cieciura, Olga Gewartowska, Jakub Gruchota, Anna Kotrys, Vladyslava Liudkovska, Seweryn Mroczek, Roman Szczęsny, Rafał Tomecki, Zbigniew Warkocki

Alumni: Maciej Aleksander, Karolina Drążkowska, Weronika Jonko, Katarzyna Kalisiak, Anna Łabno, Jacek Miłek, Aleksandra Siwaszek, Teresa Szczepińska, Marta Ukleja, Róża Węglińska, Magdalena Wójcik

Selected publications:

Tomecki R, Drazkowska K, Kucinski I, Stodus K, Szczesny RJ, Gruchota J, Owczarek EP, Kalisiak K, Dziembowski A. Multiple myeloma-associated hDIS3 mutations cause perturbations in cellular RNA metabolism and suggest hDIS3 PIN domain as a potential drug target. Nucleic Acids Res. 2013 Epub ahead of print

Lubas M, Damgaard CK, Tomecki R, Cysewski D, Jensen TH, Dziembowski A. Exonuclease hDIS3L2 specifies an exosome-independent 3′-5′ degradation pathway of human cytoplasmic mRNA. EMBO J. 2013 Jul 3;32(13):1855-68.

Drazkowska K, Tomecki R, Stodus K, Kowalska K, Czarnocki-Cieciura M, Dziembowski A. The RNA exosome complex central channel controls both exonuclease and endonuclease Dis3 activities in vivo and in vitro. Nucleic Acids Res. 2013 Apr 1;41(6):3845-58.

Borowski LS, Dziembowski A, Hejnowicz MS, Stepien PP, Szczesny RJ. Human mitochondrial RNA decay mediated by PNPase-hSuv3 complex takes place in distinct foci. Nucleic Acids Res. 2013 Jan;41(2):1223-40.

Peña A*, Gewartowski1 K*, Mroczek M, Cuéllar J, Szykowska A, Prokop A, Czarnocki-Cieciura M, Piwowarski J, Tous C, Aguilera A, JCarrascosa JL, Valpuesta JM, Dziembowski A, Architecture and nucleic acids recognition mechanism of the THO complex, an mRNP assembly factor. EMBO J, 21;31(6):1605-16 *equally contributed

Lubas M, Christensen MS, Kristiansen MS, Domanski M, Falkenby LG, Lykke-Andersen S, Andersen JS, Dziembowski A*, Jensen TH*: Interaction profiling identifies the human nuclear exosome targeting complex. Mol Cell 2011, 43(4):624-637. *corresponding authors

Tomecki R, Kristiansen MS, Lykke-Andersen S, Chlebowski A, Larsen KM, Szczesny RJ, Drazkowska K, Pastula A, Andersen JS, Stepien PP, Dziembowski A*, Jensen TH* The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L. EMBO J 2010, 29(14):2342-2357. *corresponding authors

Lebreton A#, Tomecki R#, Dziembowski A*, Seraphin B*: Endonucleolytic RNA cleavage by a eukaryotic exosome. Nature 2008, 456(7224):993-996. # equally contributed *corresponding authors

Lorentzen E, Basquin J, Tomecki R, Dziembowski A, Conti E: Structure of the active subunit of the yeast exosome core, Rrp44: diverse modes of substrate recruitment in the RNase II nuclease family. Mol Cell 2008, 29(6):717-728.

Dziembowski A*, Lorentzen E, Conti E, Seraphin B*: A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol 2007, 14(1):15-22. *corresponding authors

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