The archaeology of coding RNA

Different theories concerning the origin of RNA (and, in particular, mRNA) point to the concatenation and expansion of proto-tRNA-like structures. Different biochemical and biophysical tools have been used to search for ancient-like RNA elements with a specific structure in genomic viral RNAs, including that of the hepatitis C virus, as well as in cellular mRNA populations, in particular those of human hepatocytes. We define this method as archaeological, and it has been designed to discover evolutionary patterns through a nonphylogenetic and nonrepresentational strategy. tRNA-like elements were found in structurally or functionally relevant positions both in viral RNA and in one of the liver mRNAs examined, the antagonist interferon-alpha subtype 5 (IFNA5) mRNA. Additionally, tRNA-like elements are highly represented within the hepatic mRNA population, which suggests that they could have participated in the formation of coding RNAs in the distant past. Expanding on this finding, we have observed a recurring dsRNA-like motif next to the tRNA-like elements in both viral RNAs and IFNA5 mRNA. This suggested that the concatenation of these RNA motifs was an activity present in the RNA pools that might have been relevant in the RNA world. The extensive alteration of sequences that likely triggered the transition from the predecessors of coding RNAs to the first fully functional mRNAs (which was not the case in the stepwise construction of noncoding rRNAs) hinders the phylogeny-based identification of RNA elements (both sequences and structures) that might have been active before the advent of protein synthesis. Therefore, our RNA archaeological method is presented as a way to better understand the structural/functional versatility of a variety of RNA elements, which might represent the losers in the process of RNA evolution as they had to adapt to the selective pressures favoring the coding capacity of the progressively longer mRNAs.