Scientists at Cornwell University have found that messenger RNAs (mRNAs) contain chemical marks that are critical for protecting cells from viruses. The results of a study published in Nature suggest that erroneous modifications of RNA molecules may underlie some autoimmune and inflammatory diseases.
Mature messenger RNA is an RNA molecule whose nucleotide sequence corresponds to the nucleotide sequence of a particular gene, which encodes the amino acid sequence of the corresponding protein. In a process called translation, mRNA carries genetic information from the nucleus of the cell to the cytosol, to the ribosomes, where protein synthesis takes place. An important role is played by additional molecules that bind to mRNA and regulate translation, for example, methyl groups.
In their previous work, the scientists developed methods for detecting one of the methyl modifications, methyladenosine, or m6A, which controls the stability of mRNA in cells. Changes in this modification can lead to different types of cancer. However, another modification, Cap 2, is sometimes found in mRNA, which is methylation at the second nucleotide of the RNA chain.
Using the new CLAM-Cap-seq RNA sequencing method, the researchers found that Cap2 methylation can occur on any mRNA, but is relatively slow, so that it is usually only detected on mRNAs that have been in the cytosol for longer periods of time. The function of Cap2, which provides additional antiviral protection, is opposite to that of Cap1, which is the methylation of the first nucleotide. When mRNAs have only Cap1, their ability to trigger cellular antiviral mechanisms is sharply reduced.
However, an excess of Cap2 also has a negative effect, since it increases the likelihood that the RNA of viruses will begin to acquire this modification, protecting them from immune attack and allowing viruses to multiply uncontrollably.