AND ME
Washington, December 8
Apart from the skin, the digestive tract is the tissue that is most exposed to environmental influences, such as bacteria and viruses. Therefore, the cells that form these barriers inside the body also have special defense mechanisms.
A research team led by Professor Dr. Thorsten Hoppe has now shown that RNA interference, or RNAi for short, which is known to be a viral defense mechanism, also prevents cells from overproducing the body’s own proteins. intestinal. The study ‘ER-associated RNA silencing promotes ER quality control’ has been published in the journal Nature Cell Biology.
RNAi is able to recognize, bind, and ultimately degrade the RNA of viruses. This prevents the production of viral proteins. With the help of green fluorescent proteins and subsequent analysis in the Caenorhabditis elegans nematode, the UoC research team has been able to show that RNAi also intervenes in cells during protein production to maintain protein balance (protein homeostasis) of cells. intestinal cells.
The production of the body’s own proteins begins with the copying of DNA and the creation of the template molecule, also known as messenger RNA (mRNA), in the cell nucleus. The mRNA is then delivered to the endoplasmic reticulum (ER), where a protein is produced from the template molecule. As in a factory, the manufactured proteins are subject to strict quality control. Deficient proteins are exported from the ER and degraded to avoid cell wastage and extensive negative consequences for cell as well as tissue physiology and functionality.
“We observed that the RNAi mechanism specifically degrades messenger RNAs in the ER even before the protein is produced. This serves to prevent the ER from becoming overloaded with too much production,” said Dr. Franziska Ottens, one of the study’s first authors. The scientists thus found a new mechanism to regulate protein production.
The interaction between RNAi and previously known ER quality control systems appears to be important for overall gut health. This is demonstrated by the fact that the simultaneous failure of both mechanisms affects the important barrier function of the intestine. The study results also suggest a link between ER functionality and quality control, which are important for protection against viral infection. For example, RNA viruses like SARS-CoV use the ER for replication.
“We were able to significantly suppress viral loads by specifically overloading the ER. The interplay of protein homeostasis, RNAi and viral infection could be an important focus for prospective investigation and treatment of viral diseases,” said PhD candidate Sotirios Efstathiou, a member of Thorsten Hoppe’s team and another first author. of the study.
