A Spanish scientific team has created a procedure to look for ancient elements in the current RNA and understand the first phases of life as we know it. The results could contribute to the investigation of pathogenic viruses such as hepatitis C.
An investigation carried out by three teams of the Higher Council of Scientific Research (CSIC) aims to dig up the lost structural elements of ribonucleic acid (RNA), which were functional in the past, to understand the first phases of biochemical evolution of complex life.
In collaboration with the Center for Biomedical Research in Network for Liver and Digestive diseases (Carlos III Health Institute, CIBEREHD), the study is published on the cover of the Annals of New York Academy of Sciences.
Scientists have devised a new method to search in the current RNA for elements of the old RNA that have been repressed, blurred or reorganized throughout evolution. The procedure, called archeology of the coding RNA, could have applications in virology, since it opens the door to find small molecules capable of preventing the replication of certain pathogenic viruses, such as hepatitis C.
The researchers propose to study the molecular past of messenger RNA (mRNA), the single-chain ribonucleic acid that transfers the information contained in cellular DNA to proteins. The objective is to determine if these coding RNA molecules hide in their interior structural elements capable of being recognized by current enzymes with archaic origins and if they form patterns.
“All these factors refer in one way or another to the remote past of life within the stage of its origin, which we know as ‘the world of RNA’. It is, therefore, to describe the evolutionary history of RNA by observing it with ‘enzyme eyes’. In this way, we work as the archaeologist who explores the remote past and interprets it based on the objects found in the oldest strata,” explains researcher Jordi Gómez, who has led this work from the López Neyra Institute of Parasitology and Biomedicine.
Using this method, Gomez’s team found, among other results, that the antibiotic geneticin also inhibits hepatitis C virus replication in infected cells.
Researchers have identified small structural elements of RNA that, at the stage of the origin of life, could have circulated freely, being then integrated into larger RNA molecules with coding capacity (after the fixation of the genetic code): the RNAs current cellular and viral messengers.
The objective, therefore, is to open a door to understanding the evolution of RNA from the point of view of ‘losers’ in the process. Both during the concatenation of those primitive circulating elements, and in their subsequent participation in the coding necessary for protein synthesis, they would have lost many of their original degrees of evolutionary and functional freedom.
The factors used by the scientists in the study – the ‘toolbox’ – have been human and bacterial ribozyme (RNA enzyme), and the Ribonuclease III enzyme of Escherichia coli bacteria . In addition, they have studied ultraviolet C (UV-C) radiation, which is capable of activating specific autoscission in some local tertiary RNA structures. The field studied has been the set of hepatocyte mRNA, genomic RNA (which functions as mRNA) of hepatitis C virus and other evolutionarily related viruses.
“It is a method, alternative and complementary to molecular phylogeny, to search for and identify RNA elements from the past, regardless of whether their sequences have blurred and their function has changed,” says another of the authors of the work, the Esteban Domingo researcher, from the Severo Ochoa Molecular Biology Center (mixed center of the CSIC and the Autonomous University of Madrid).
With the tests carried out, scientists have analyzed the ability of RNA to recognize or be recognized by the factors studied, which provides direct information on the material aspects (such as composition, molecular patterns, catalytic activity or location) of ancient RNAs.
“The difference between the evolutionary research system that we have developed and the conventional phylogenetic methods is clear, since they base their analysis on representations, on comparing the RNA base sequences, which basically are nothing more than maps and plans of their structures,” said another of the authors of the work, the researcher Carlos Briones, of the Astrobiology Center (mixed of the CSIC and INTA)