Katja Petzold

The human genome encodes> 1700 microRNA (miRNA), which controls at least 30% of all proteins expressed. Unregulated miRNA has been found in> 50% of all forms of cancer and thus plays a central role in the development of cancer. Understanding miRNA function and structure is crucial for understanding cancer regulation. The microRNA miR34a, studied in this project, regulates many cancer-related proteins, e.g. Sirt1, CD44, BCL2. A major problem in the current structure determining methods is that it is used in simplified environment, water with small salt. We want to study microRNA structure and regulation in living cells. We use nuclear magnetic resonance (NMR) to illuminate miRNA-mRNA interaction in in vitro environment and in living cells. In addition, we will use biophysical methods to study RNA, e.g. EMSA, UV fusion, fluorescence-based interaction studies, to investigate the structure of miR-34a with different target RNAs in vitro and in living cells. This will lead to a hypothesis of which structure is active with a focus on a specific mRNA under certain environment. We will examine this conformation with modifications on miR-34a and test this structure, in collaboration, about their function in cells and in mice. Since structural change in RNA can control cancer development, this is likely to reveal a whole new level of adjustment of miRNA activities. My research will help to understand the selection process of miRNAs as cancer regulators and therefore will generate important information necessary for innovative development of miRNA tools for cancer and pharmaceutical research. Insights The dynamics of base pairing facilitate predicting other miRNA mRNA complexes and their motions. There is already a miR 34a analog, which is tested in clinical phase 1. Unfortunately, it is unknown how miR 34a is selected for its target mRNA and can therefore create many side effects.

The human genome encodes> 1700 microRNA (miRNA), which controls at least 30% of all proteins expressed. Unregulated miRNA has been found in> 50% of all forms of cancer and thus plays a central role in the development of cancer. Understanding miRNA function and structure is crucial for understanding cancer regulation. The microRNA miR 34a, studied in this project, inactivates the cancer suppressor protein p53 via deacetylation of SIRT1. The mechanism of miR 34a inhibition is not entirely clear due to lack of structural and dynamic information, but to study movement and explain their functions requires observation as in a "movie". We use nuclear magnetic resonance (NMR) to illuminate miRNA-mRNA interaction. This is based on base pair energetics and alternative structure formation and allows fine tuning of miRNA based regulation of translation of cancer-related proteins, such as miR 34a. MiR-34a regulates p53, which has a key role in slowing down cancer. We analyze miRNA mRNA complexes that regulate P53's activity through structural changes. Furthermore, miR 34a has> 50 target mRNA, but it is not understood which mRNA is regulated at any time. We study with NMR, biochemical and in vivo methods how miR 34a selects its correct target from a pool of mRNA (eg, CD44, Jagged, Notch) As structural change in RNA can control cancer development, this is likely to reveal a whole new level of miRNA activity adjustment. My research will help to understand the selection process of miRNAs as cancer regulators and therefore will generate important information necessary for innovative development of miRNA tools for cancer and pharmaceutical research. Insights The dynamics of base pairing facilitate predicting other miRNA-mRNA complexes and their motions. There is already a miR-34a analog, which is tested in clinical phase 1. Unfortunately, it is unknown how miR-34a is selected for its target mRNA and can therefore create many side effects.

The human genome encodes> 1700 microRNA (miRNA), which controls at least 30% of all proteins expressed. Unregulated miRNA has been found in> 50% of all forms of cancer and thus plays a central role in the development of cancer. Understanding miRNA function and structure is crucial for understanding cancer regulation. The microRNA miR 34a, studied in this project, inactivates the cancer suppressor protein p53 via deacetylation of SIRT1. The mechanism of miR 34a inhibition is not entirely clear due to lack of structural and dynamic information, but to study movement and explain their functions requires observation as in a "movie". We use nuclear magnetic resonance (NMR) to illuminate miRNA-mRNA interaction. This is based on base pair energetics and alternative structure formation and allows fine tuning of miRNA based regulation of translation of cancer-related proteins, such as miR 34a. MiR-34a regulates p53, which has a key role in slowing down cancer. We analyze miRNA mRNA complexes that regulate P53's activity through structural changes. Furthermore, miR 34a has> 50 target mRNA, but it is not understood which mRNA is regulated at any time. We study with NMR, biochemical and in vivo methods how miR 34a selects its correct target from a pool of mRNA (eg, CD44, Jagged, Notch) As structural change in RNA can control cancer development, this is likely to reveal a whole new level of miRNA activity adjustment. My research will help to understand the selection process of miRNAs as cancer regulators and therefore will generate important information necessary for innovative development of miRNA tools for cancer and pharmaceutical research. Insights The dynamics of base pairing facilitate predicting other miRNA-mRNA complexes and their motions. There is already a miR-34a analog, which is tested in clinical phase 1. Unfortunately, it is unknown how miR-34a is selected for its target mRNA and can therefore create many side effects.

The human genome encodes> 1700 microRNA (miRNA), which controls at least 30% of all proteins expressed. Unregulated miRNA has been found in> 50% of all forms of cancer and thus plays a central role in the development of cancer. Understanding miRNA function and structure is crucial for understanding cancer regulation. The microRNA miR 34a, studied in this project, inactivates the cancer suppressor protein p53 via deacetylation of SIRT1. The mechanism of miR 34a inhibition is not entirely clear due to lack of structural and dynamic information, but to study movement and explain their functions requires observation as in a "movie". We use nuclear magnetic resonance (NMR) to illuminate miRNA-mRNA interaction. This is based on base pair energetics and alternative structure formation and allows fine tuning of miRNA based regulation of translation of cancer-related proteins, such as miR 34a. MiR-34a regulates p53, which has a key role in slowing down cancer. We analyze miRNA mRNA complexes that regulate P53's activity through structural changes. Furthermore, miR 34a has> 50 target mRNA, but it is not understood which mRNA is regulated at any time. We study with NMR, biochemical and in vivo methods how miR 34a selects its correct target from a pool of mRNA (eg, CD44, Jagged, Notch) As structural change in RNA can control cancer development, this is likely to reveal a whole new level of miRNA activity adjustment. My research will help to understand the selection process of miRNAs as cancer regulators and therefore will generate important information necessary for innovative development of miRNA tools for cancer and pharmaceutical research. Insights The dynamics of base pairing facilitate predicting other miRNA-mRNA complexes and their motions. There is already a miR-34a analog, which is tested in clinical phase 1. Unfortunately, it is unknown how miR-34a is selected for its target mRNA and can therefore create many side effects.