RNA based regulation of Gene Expression – Peter Lukavsky

• Molecular principles of posttranscriptional regulation of gene expression through alternative splicing, RNA transport and translational control
• 3D structure determination of large RNAs and RNA-protein complexes by solution NMR spectroscopy
• Biochemical and biophysical studies of RNA-protein interactions
• Development of novel purification methods and isotope labelling schemes for NMR studies of large RNAs and their assemblies

• Molecular basis of spatial and temporal control of gene expression through directed RNA transport in dendrites and during development
• Investigation of molecular principles of RNA-protein interaction networks regulating alternative mRNA splicing of disease-related genes
• Advancing the size of RNAs and their assemblies amenable to solution NMR studies

Post-transcriptional regulation of gene expression is based on regulatory RNA elements which determine the protein sequence of a gene product through pre-mRNA alternative splicing in the nucleus and control temporal and spatial pattern of protein synthesis in the cytoplasm.  While we begin to decipher the splicing code, only very little is known about how mRNAs reach their cellular compartments to ensure that proteins are expressed in the right place at the right time within the cell.  This compositional, spatial and temporal control of gene expression is key for maintaining the order of events during development and for local response to stimuli in specialized cells such as neurons and, thus, deregulation often leads to human disease.

Our aim is to unravel molecular principles governing post-transcriptional regulation of gene expression.  Using NMR spectroscopy as our main structural tool, we will study RNA-protein (RNP) interaction networks regulating alternative splicing of disease-related genes and RNA elements and their protein assemblies crucial for control of protein synthesis in the cytoplasm.

At CEITEC, we are in a good position to tackle these large biological RNP systems with the excellent high-field NMR equipment in place and since we pioneered NMR structure determination of large RNA systems in the past.  Our NMR structural work is always complemented with biochemistry, x-ray crystallography, other biophysical methods and cell biology to create a comprehensive molecular description of RNP function.  Failure to properly splice mRNAs and to transport them into the right cellular compartment can lead to impairment of memory formation and severe human diseases.  Molecular insights into mechanisms governing RNA-based regulation of gene expression is therefore fundamentally important for understanding neurobiology, neurological disorders and human disease, and is key for the development of successful therapies in the future.

Post-transcriptional regulation of gene expression is based on regulatory RNA elements which determine the protein sequence of a gene product through pre-mRNA alternative splicing in the nucleus and control temporal and spatial pattern of protein synthesis in the cytoplasm.  While we begin to decipher the splicing code, only very little is known about how mRNAs reach their cellular compartments to ensure that proteins are expressed in the right place at the right time within the cell.  This compositional, spatial and temporal control of gene expression is key for maintaining the order of events during development and for local response to stimuli in specialized cells such as neurons and, thus, deregulation often leads to human disease.

Our aim is to unravel molecular principles governing post-transcriptional regulation of gene expression.  Using NMR spectroscopy as our main structural tool, we will study RNA-protein (RNP) interaction networks regulating alternative splicing of disease-related genes and RNA elements and their protein assemblies crucial for control of protein synthesis in the cytoplasm.

At CEITEC, we are in a good position to tackle these large biological RNP systems with the excellent high-field NMR equipment in place and since we pioneered NMR structure determination of large RNA systems in the past.  Our NMR structural work is always complemented with biochemistry, x-ray crystallography, other biophysical methods and cell biology to create a comprehensive molecular description of RNP function.  Failure to properly splice mRNAs and to transport them into the right cellular compartment can lead to impairment of memory formation and severe human diseases.  Molecular insights into mechanisms governing RNA-based regulation of gene expression is therefore fundamentally important for understanding neurobiology, neurological disorders and human disease, and is key for the development of successful therapies in the future.