Dr. Markus Hafner on the importance of RNA and RNA-binding proteins in gene expression and disease.

Dr. Markus Hafner on the importance of RNA and RNA-binding proteins in gene expression and disease.


DR. MARKUS HAFNER: It is remarkable how one single cell of the fertilized egg gives rise to millions of daughter cells sharing the same genetic information but appearing differently and functioning differently. These differences arise due to the use of specific genes at specific times and in a process called gene expression, which starts with a transcription of DNA into a molecule called RNA, and then further which is translated into a molecule called proteins. And RNA itself is not just a passive carrier of genetic information, but also a point of intense regulation. Our research reveals clues on how regulation on the RNA level impacts germline development, and a number of transcription factors controlling the production of RNA during germline development are very well characterized. However, in the cells that will become the germline, there is already RNA present that may need to be cleared in order to ensure precise developmental transitions. And we think that we found one of those factors responsible for clearance of RNA. We found the Dead-end 1 (DND1), which is known to be necessary for the development and maintenance of the germline, is an RNA-binding protein that may be necessary for the clearance of unwanted RNA in the cells. Dead-end 1 (DND1) binds to very specific sequences on RNA and recruits a large molecular machinery that degrades RNA. And mice that are lacking Dead-end 1 (DND1) have two problems. They develop testicular germ cell tumors, a caner, and they are sterile. So the sterility is due to the loss of germline stem cells, which give rise to sperm and egg in a process called apoptosis, which is a form of cell death. And at the same time, a few of these cells survive, and these cells start dividing uncontrollably and give rise to the testicular germ cell tumors. By studying Dead-end 1 (DND1), we think we’ve found the molecular mechanisms underlying two conditions and diseases, such as cancer and sterility. So our main goal is the understanding of how RNA-binding proteins regulate gene expression by influencing RNA, in this case, with a focus on RNA stability. So the main takeaway is that RNA is not just a passive messenger carrier of genetic information, as in the sequence, DNA codes for RNA, codes for proteins, but that at the same time, it is heavily regulated. And when this regulation goes wrong, a number of conditions and disorders can occur, including cancer and sterility, but also muscular dystrophy and a number of neurological diseases. That’s why the research we are conducting is so important, as it gives us mechanistic insights into these diseases and conditions.

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