PHILADELPHIA -- The cells in our body are home to thousands of tiny molecules called RNAs. There are many different types of RNAs – some carry the code for specific proteins to be made, some transport things within the cell, and some can influence which genes get turned on or off. New RNAs and their functions are still being discovered. Researchers in the lab of Isidore Rigoutsos, PhD in the Computational Medicine Center at Thomas Jefferson University described new properties for a little known class of RNAs called “ribosomal RNA-derived fragments,” or rRFs.
(Watch an animated illustration of what the researchers found.)
The researchers analyzed samples from around 450 healthy individuals who participated in the 1000 Genomes Project, an international effort to catalog genetic variants in human populations. The samples originated from 5 different populations around the world. The analysis focused on a group of approximately 50,000 molecules that derive from ribosomal RNA (rRNA). These rRNA-derived fragments had initially been thought to be byproducts of waste and degradation. “In fact, we discovered that this large class of short regulatory RNAs are produced in a regimented manner,” says Tess Cherlin, PhD candidate and first author of the study. Of the thousands of rRFs found, many were present in all the samples. However, a significant number of rRFs seemed dependent on certain attributes of the individual. “We found that the presence of this type of RNA is influenced by whether the person is male or female, or their population of origin,” says Tess.
“The finding and the sheer number of rRFs has given us pause. For many years, the field assumed that the same short piece of DNA, which is the starting material for RNA, will produce the same short RNA in all people. Our work in the last nearly ten years has shown that this could not be further from the truth,” says Dr. Rigoutsos. “Initially, we found that the abundances of isomiRs, the isoforms of microRNAs, depend on personal attributes. Then, we found that the same dependency holds for the abundances of the tRFs, the short fragments that derive from transfer RNA. And, now, we find the same to be true for the rRFs as well.”
This finding is important in the context of disease susceptibility; many diseases affect people differently based on the abundance, high or low, of certain proteins. There is emerging evidence that rRFs can regulate how much protein a cell produces, just like the isomiRs and tRFs. This regulatory control can be altered in some diseases, and either too much or too little protein is made. Therefore, it is very important for scientists to understand what the cell’s normal levels of these short RNAs are in order to know how they are changed by disease. This new research shows that these normal levels are different in people who differ by sex or population of origin.
“It’s too early to know how similar rRFs are to microRNAs in terms of mechanism of action,” says Dr. Rigoutsos. “But their identification is a very important first step in understanding how rRFs contribute to the complexity of our genetic profile, and may be important for predicting diseases sooner and designing personalized therapies.”
The study was published in BMC Biology.