Cell: scientists have identified a new molecular mechanism behind the body's immune response

December 7, 2019 / BIOON / -- recently, an international magazine was published in cell In the previous research report, scientists from the University of Munich and other institutions in Germany found that a central component of innate immune response can be activated by two short chain RNAs, which are produced by site-specific cleavage of precursor RNA molecules, and their derivatives can also be produced by the same enzymes Image source: imageimages / westend61 Innate immune response is often considered as the first line of defense against foreign pathogens Cells have special receptors, which can distinguish the RNAs produced by exogenous cells from their own After recognizing the exogenous RNAs, the appropriate immune response of the body will be activated to clear the invaders However, at present, researchers do not know the molecular mechanism behind it; this study Through joint research, the researchers found that the activation of a receptor named tlr8 can be mediated by binding to two special RNA segments (produced by exogenous RNA degradation), and the fragmentation products of exogenous RNA can also be produced by a single enzyme named RNase T2 According to Hornung, previous studies have shown that exogenous RNA molecules are not considered as a whole, and must be cut into small pieces before they are recognized by the innate immune system of the body In order to further clarify the mechanism of innate immune system recognition, researchers removed a single RNases gene from the human cell model, and then analyzed each RNases missing How to affect tlr8 activation? Tlr8 is considered to be an important sensor of bacterial RNA in human cells Researchers choose to study the human cell model, because in the mouse body, the receptor version will play a role in a different way The researchers found that only cells without RNase T2 gene expression could not induce bacterial RNA response mediated by tlr8, which elucidated the important role of this enzyme in the activation of receptor expression; it is worth noting that enzymes like RNase T2 is highly conserved in the process of evolution, in fact, it exists in all organisms, and its structure has not changed; this highly conserved structure shows that T2 can play the most basic cell function, and its mechanism plays an important role in other species Now we have identified RNase by mass spectrometry, said researcher Mirko Wagner It is a special product of T2 split RNA Relevant research results show that this kind of enzyme can preferentially cut special RNA molecules (i.e the determined nucleotide sequence can induce the degradation products that only activate tlr8): uridine and purine terminate RNA segments; in essence, these receptors contain two different groove structures, each groove structure is occupied to be activated, and one groove can be activated However, in the physiological context, activation depends on the previous binding with purine termination RNA fragment, which can promote the binding of uridine; activation of these two steps and RNase T2 can provide key activation information; the researchers believe that in the process of evolution, the receptor can specifically adapt to and recognize the degradation products of enzymes Original source: Wilhelm Greulich, Mirko Wagner, Moritz M gaidt, et al Tlr8 is a sensor of RNase T2 graduation products, cell (2019) Doi: 10.1016/j.cell.2019.11.001