Stamm laboratory:
Alternative pre-mRNA processing and human disease |
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Our work
The long-term aim of our research is to understand the regulation and function of alternative pre-mRNA processing, mainly alternative splicing, but also regulation of RNA stability, and the formation of circular RNAs. We apply the knowledge gained in designing therapies against diseases caused by errors in RNA processing, such as Prader-Willi syndrome and Alzheimer’s disease.
Alternative pre-mRNA processing and alternative splicing in disease
In higher eukaryotes, genes are interrupted by intervening sequences (introns). After the DNA of a gene is copied into pre-mRNA, these intronic sequences have to be removed and the remaining sequences (exons) are joined. This process is known as pre-mRNA splicing. Often, a cell can alternatively include or exclude a sequence from the mature mRNA, a process that is known as alternative splicing.
In higher eukaryotes, genes are interrupted by intervening sequences (introns). After the DNA of a gene is copied into pre-mRNA, these intronic sequences have to be removed and the remaining sequences (exons) are joined. This process is known as pre-mRNA splicing. Often, a cell can alternatively include or exclude a sequence from the mature mRNA, a process that is known as alternative splicing.
Alternative splicing is an important mechanism to create protein diversity. It allows to create more than one protein from a given pre-mRNA, or to switch off the protein by including a stop codon in its mRNA. Alternative splicing pathways are not static, but subject to changes e.g. in development, or in response to outside stimuli. Numerous examples of alternative splicing have been observed in the brain, where this mechanism might contribute to neuronal plasticity.
Current projects
We are funded from the NIH, the Department of Defense, the Binational Science Foundation and the Foundation for Prader-Willi Research to work on these projects:
1. Role of circular RNAs in Alzheimer’s disease
We are testing whether human-specific circular RNAs generate fragments of the microtubule-associated protein tau that act as seeds to form tau deposits leading to Alzheimer's disease.
2. Role of non-coding RNAs (snoRNAs) in Prader-Willi syndrome
We are finding target genes for orphan C/D box snoRNAs missing in Prader-Willi syndrome and develop oligonucleotides for their substitution to treat hyperphagia and defects in hormonal release.
3. Changing alternative splicing of the serotonin receptor 2C to combat spasticity and obesity
We are testing oligonucleotides resembling C/D box snoRNAs missing in Prader-Willi syndrome for their effects on spasticity after spinal cord injury.
1. Role of circular RNAs in Alzheimer’s disease
We are testing whether human-specific circular RNAs generate fragments of the microtubule-associated protein tau that act as seeds to form tau deposits leading to Alzheimer's disease.
2. Role of non-coding RNAs (snoRNAs) in Prader-Willi syndrome
We are finding target genes for orphan C/D box snoRNAs missing in Prader-Willi syndrome and develop oligonucleotides for their substitution to treat hyperphagia and defects in hormonal release.
3. Changing alternative splicing of the serotonin receptor 2C to combat spasticity and obesity
We are testing oligonucleotides resembling C/D box snoRNAs missing in Prader-Willi syndrome for their effects on spasticity after spinal cord injury.
For more information, please go to projects.
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