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+420 54949 2614 |
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Research areas
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Mechanisms of nuclear RNA surveillance and degradation
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Mechanisms and function of noncanonical polyadenylation
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RNA uridylation and nucleotide modification
Main objectives
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Investigation of the role of RNA in development and human diseases.
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Biochemical and structural characterization of RNA in eukaryotic cells.
Content of research
RNA is essential for cell survival. It is not only a messenger between the genomes and proteomes but also carries out or participates in many functions such as RNA processing and protein translation, acting as structural scaffolds, transporters, gene regulators and biocatalysts. Eukaryotic cells produce diverse types of RNAs. Most, if not all, are synthesized in a form of a precursor that needs to be post-transcriptionally processed and/or modified in order to form mature functional molecules. In yeast, the nuclear RNA maturation and stability is under the strict control of RNA surveillance by the nuclear exosome and its cofactors the TRAMP4 and TRAMP5 noncanonical polyadenylation complexes and the Nrd1 RNA binding complex.
We aim to clarify molecular mechanisms underlying RNA quality control and degradation in eukaryotic cells through the investigation of the detailed biochemical principles of RNA recognition, processing and degradation. These include (1) in-depth characterization of the biochemistry of the TRAMP4 and exosome complexes; (2) examination of the interplay among the exosome, TRAMP and Nrd1 complexes; (4) structural and biochemical characterization of proteins involved the recognition of aberrant RNAs in eukaryotic cells; (5) integration of the knowledge obtained from yeast systems to investigate mechanisms and functions of noncanonical polyadenylation and uridylation in mammalian cells. The combined knowledge from the yeast noncanonical polyadenylation and from the mammalian terminal uridylation will significantly improve our understanding of eukaryotic pathways regulating gene expression via noncoding RNAs. We use a combination of biochemical, genetic, and structural methods to unravel the molecular mechanism of the eukaryotic RNA surveillance.
CURRENT RESEARCH INFRASTRUCTURE
The research group is currently equipped with the instrumentation for bacterial, yeast and mammalian cell culture, DNA, RNA and protein expression and purification including HPLC and FPLC apparatuses, a deep freezer, and other basic equipment for molecular biology and biochemistry work. It has been licensed to work with ionizing radiation.
1. The role of posttranscriptional RNA modifications in disease
Supervisor: doc. Mgr. Štěpánka Vaňáčová, Ph.D.
Consultants: doc. Mgr. Richard Štefl, Ph.D.
Annotation:
RNA is essential for cell survival. It is not only a messenger between the genomes and proteomes but also carries out or participates in many functions such as RNA processing and protein translation, acting as structural scaffolds, transporters, gene regulators and biocatalysts. The recent advances in high-troughput technologies allowed for the identification of a vast repertoir of new types of RNAs and RNA modifications. The next step is to understand if there are any functional consequences of their production. Recent studies showed that production and stability of many noncoding RNAs is regulated by so called noncanonical polyadenylation and/or uridylation. In this project, we will aim to characterize machines, mechanisms and in vivo roles of noncanonical 3' terminal RNA tailing. Studies in our laboratory have previously identified several interesting protein-protein interactions between factors involved in processing, tailing and degradation. The student will use a wide spectrum of methods from basic to high advanced techniques of molecular biology and biochemistry which will be accompanied by in vivo studies in yeast and mammalian cells. It is a highly competitive project which requires highly motivated and dedicated student.
