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Institute of Genetics and Biotechnology Warsaw University (affiliated with IBB PAS)

Head: Professor Piotr Węgleński

 


Studies on genetic control of arginine metabolism in Aspergillus

Group leader: Prof. Piotr Węgleński
Staff:



Research project:

 

Selected publications:

 


Molecular functions of human SUV3 gene

Group leader: Prof. Piotr P. Stepień
Staff:

Research in my group is focused on molecular mechanisms of RNA turnover in mitochondria. The miniature mammalian mitochondrial genomes are organized in an extremely compact way; they are about 16 kbp long and encode only 13 proteins plus two ribosomal RNAs and a set of tRNAs necessary to translate the encoded subunits of the oxidative phosphorylation complexes. Disturbances in proper functioning of mitochondrial gene expression have been implicated in many human conditions including aging, cancer and neurodegenerative diseases. Thus understanding the mechanisms of mtDNA expression is of fundamental importance.

In all biological systems RNA decay plays three important roles: it determines the half-life of a given RNA species, it destroys the aberrantly formed RNA molecules which might interfere with the translation machinery, and it degrades the processing intermediates.

So far the best characterized mitochondrial RNA decay system has been described for the yeast S. cerevisiae, because both genetical and biochemical analysis was available. Our studies revealed that yeast mtRNA turnover is accomplished by the two-subunit protein complex called mtEXO or mitochondrial degradosome. It consists of an RNA helicase encoded by the nuclear gene SUV3 and of an exoribonuclease encoded by the nuclear gene DSS1. Both proteins form a complex where the helicase feeds the RNA substrate at the expense of ATP hydrolysis into the active center of DSS1 ribonuclease, and the degradation reaction proceeds from the 3’ end to 5’ end yielding nucleoside monophosphates.

At present most of our studies are focused on human mitochondrial RNA surveillance system. We have shown that it consists of the SUV3 RNA helicase and polynucleotide phosphorylase PNPase, both enzymes are encoded by the nuclear genome. We have identified the human gene responsible for mtRNA polyadenylation and several interacting proteins of the SUV3 helicase: WRN, BLM and HBXIP.

Research grants:

2008-2011 "Anti-cancer drug based on anti-apoptotic functions of the SUV3 protein", (Ministry of Sciences
                   and Higer Education)

 

Selected publications:

 

 


Analysis of mitochondrial polymorphisms in the Polish population

Group leader: Prof. Ewa Bartnik
Staff:

 

Human mitochondrial DNA (mtDNA) is a circular molecule of 16.5 kb encoding 37 of the over 1000 genes necessary for mitochondrial function; the remaining ones are encoded in the nucleus. The 37 genes present in mitochondrial DNA are responsible for the production of 13 mitochondrial proteins, forming parts of complexes I, III, IV and V of the respiratory chain and 2 rRNAs and 22 tRNAs required for mitochondrial translation. There are very few non-coding sequences in human mtDNA, the largest one is the so-called D-loop of over 1 kb, which is also the most variable part of mitochondrial DNA. Mitochondria are maternally inherited, and mutations in the mtDNA lead to a number of human diseases, mainly affecting the muscle and nerve systems, including a form of blindness called Leber hereditary optic neuropathy.

Mitochondrial DNA has been extensively studied in human populations and sequences which are related have been grouped into haplogroups, representing mtDNAs derived from a recent common ancestral sequence. All are of course derived from the ancestral “mitochondrial Eve” sequence.

Initially all haplogroups have been considered as not differing in any functional way; in recent years, however, associations of various diseases, longevity and cancer with particular haplogrups have been described in the literature.

The interest of our group in mitochondrial diseases led us to analyze the mitochondrial haplogroups in Poland, and their frequencies were found to be typical for Europe, with haplogroups H and U as the most common. Our other research involves analysis of mitochondrial mutations in cancer cells and the analysis of the distribution of mitochondrial haplogroups in cancer patients and in persons with Leber hereditary neuropathy. We are generally interested in analysis of genotype-phenotype correlations in mitochondiral disease and in the effects of haplogroups on disease.

Current projects:

Research grants:

 

Selected publications:

  1. Czarnecka A.M., Klemba A., Krawczyk T., Zdrozny M., Arnold R.S., Bartnik E., Petros J.A. Mitochondrial NADH-dehydrogenase polymorphisms as sporadic breast cancer risk factor Oncol Rep. 2010 Feb; 23(2):531-5.
  2. Bragoszewski P., Kupryjanczyk J., Bartnik E., Rachinger A., Ostrowski J. Limited clinical relevance of mitochondrial DNA mutation and gene expression analyses in ovarian cancer. BMC Cancer. 2008 Oct 8;8:292.
  3. Toñska K., Solyga A., Bartnik E. Mitochondria and aging: innocent bystanders or guilty parties? J. Appl. Genet. 2009, 50(1): 55-62
  4. Czarnecka A., Bartnik E. Mitochondrial DNA mutations in tumors. in: Cellular Respiration and Carcinogenesis. S. P. Apte I R. Sarangarajan, red., Humana Press 2009. , p. 119-130.
  5. Czarnecka A.M., Krawczyk T., Zdrożny M., Lubiński J., Arnold R.S., Kukwa W., Scińska A., Golik P., Bartnik E., Petros J.A. Mitochondrial NADH-dehydrogenase subunit 3 (ND3) polymorphism (A10398G) and sporadic breast cancer in Poland. Breast Cancer Res Treat 2009  Mar 6 Epub ahead of print
  6. Kierdaszuk B., Jamrozik Z., Tońska K., Bartnik E., Kaliszewska M., Kamińska A., Kwieciński H. Mitochondrial cytopathies: clinical, morphological and genetic characteristics. Neurol Neurochir Pol. 2009 May-Jun;43(3):216-27.
  7. Czarnecka A.M., Klemba A., Semczuk A., Plak K., Marzec B., Krawczyk T., Kofler B., Golik P., Petros J.A., Bartnik E. Common mitochondrial polymorphisms as risk factor for endometrial cancer Int Arch Med, Oct 28;2(1):33.
  8. Tonska K., Kurzawa M., Ambroziak A.M., Korwin-Rujna M., Szaflik J.P., Grabowska E., Szaflik J., Bartnik E. A family with 3460G>A and 11778G>A mutations and haplogroup analysis of Polish Leber hereditary optic neuropathy patients. Mitochondrion. 2008 Dec; 8(5-6):383-8. Epub 2008 Aug 29.

Metabolism of mitochondrial RNAs in S. cerevisiae

Group leader: Dr. Paweł Golik
Staff: M.Sc. Olga Puchta – Ph.D student

 

The aim of the project is to gain insights into mechanisms of post-transcriptional regulation of gene expression, such as RNA processing, splicing, degradation, and RNA surveillance in the mitochondria of model yeast – Saccharomyces cervisiae. Additionaly we are interested in the systems biology approach to the mitochondrial genetic system.

Post-transcriptional mechanisms, in many aspects different from those known for the nuclear genes, constitute the key steps of mitochondrial gene regulation. We are identyfying and characterizing nuclear-encoded factors involved in the RNA metabolism in mitochondria. The function of many such factors is still poorly understood. Recently, we characterized DMR1  - a gene encoding a previously unknown mitochondrial ribosmoal RNA stability factor. We are also working on the yeast mitochondrial ribonucleases – the 3’-5’ exoribonuclease complex mtEXO and a 5’-3 exoribonuclease Pet127p.

 

Selected publications:

  1. Puchta, O., Lubas, M., Lipinski, K.A., Piatkowski, J., Malecki, M., Golik, P. DMR1 (CCM1/YGR150c) of Saccharomyces cerevisiaeGenetics, (2010), art. przyjęty do druku (decyzja z dn. 22.01.2010, in press)
  2. Lipinski, K., Kaniak-Golik, A., Golik, P. Maintenance and expression of the S. cerevisiae mitochondrial genome - from genetics to evolution and systems biology. Biochim Biophys Acta - Bioenergetics, (2010) artykuł w druku, dostępny online (DOI 10.1016/j.bbabio.2009.12.019)
  3. Malecki, M., Stepien, P.P.,  Golik, P. Assays of the helicase, ATPase and exoribonuclease activities of the yeast mitochondrial degradosome. w Helicases. Methods and Protocols. Series: Methods in Molecular Biology, (2010) Vol. 587, Abdelhaleem, Mohamed M. (red.), Humana Press
  4. Malecki, M., Jedrzejczak, R., Puchta, O., Stepien, P.P.,  Golik, P. In vivo and in vitro approaches for studying the yeast mitochondrial RNA degradosome complex. Methods Enzymol (2008) 447: 463-488
  5. Małecki, M., Jędrzejczak, R., Stępień, P. P., Golik, P.. In vitro reconstitution and characterization of the yeast mitochondrial degradosome complex unravels tight functional interdependence. J Mol Biol (2007) 372: 23-36
  6. Szczepanek, T., Gora, M., Monteilhet, C., Wysocka, M., Lazowska, J., Golik, P. In vivo analysis of the relationships between the splicing and homing activities of a group I intron-encoded I-ScaI/bi2-maturase of Saccharomyces capensis produced in the yeast cytoplasm. FEMS Yeast Res (2006) 6: 823-835
  7. Rogowska, A. T., Puchta, O., Czarnecka, A. M., Kaniak, A., Stępień, P. P., Golik, P. Balance between transcription and RNA degradation is vital for Saccharomyces cerevisiae mitochondria: reduced transcription rescues the phenotype of deficient RNA degradation. Mol Biol Cell (2006) 17: 1184-1193
  8. Golik, P., Bonnefoy, N., Szczepanek, T., Saint-Georges, Y. , Lazowska, J. The Rieske FeS protein encoded and synthesized within mitochondria complements a deficiency in the nuclear gene. Proc Natl Acad Sci U S A (2003) 100: 8844-9