Origins of tmRNA: the missing link in the birth of protein synthesis?

Abstract

The RNA world hypothesis refers to the early period on earth in which RNA was central in assuring both genetic continuity and catalysis. The end of this era coincided with the development of the genetic code and protein synthesis, symbolized by the apparition of the first non-random messenger RNA (mRNA). Modern transfer-messenger RNA (tmRNA) is a unique hybrid molecule which has the properties of both mRNA and transfer RNA (tRNA). It acts as a key molecule during trans-translation, a major quality control pathway of modern bacterial protein synthesis. tmRNA shares many common characteristics with ancestral RNA. Here, we present a model in which proto-tmRNAs were the first molecules on earth to support non-random protein synthesis, explaining the emergence of early genetic code. In this way, proto-tmRNA could be the missing link between the first mRNA and tRNA molecules and modern ribosome-mediated protein synthesis.

Evolution of Nucleotide Punctuation Marks: From Structural to Linear Signals

“…tRNAs can be interpreted as a combined structural and linear signal, where the anticodon is the linear signal. tmRNAs (transfer-messenger RNA, Janssen and Hayes, 2012; Himeno et al, 2014), which rescue stalled ribosomes on mRNAs lacking proper translational stop signal also combine structural and linear signals, with extremities forming tRNA-like structures, and the rest of the sequence reminding mRNAs (Di Giulio, 2015; Macé and Gillet, 2016). This suggests that tmRNAs are remnants of ancient termination signals.…”

When transfer‐messenger RNA scars reveal its ancient origins

“…The earliest proto‐biosynthetic system would thus have originated from RNA:RNA duplexes, with the most stable complementary GC‐rich triplets coding for small polypeptides composed of alternating hydrophobic alanines and hydrophilic glycines, the first amino acids encoded . Accordingly, when comparing tmRNA resume codon sequences among bacterial species, we see that the more primitive the bacteria, the more ancestral G N C (where N is A, U, C, or G) codons are used . Three other conserved and indispensable Ala codons follow the resume codon at the 3′‐end of the internal ORF whose consensus sequence is “AN ‐ ‐ ‐ ‐ ‐ ‐ ALAA,” and this must reflect other traces of the older proto‐tmRNA.…”

“…In such a scenario, the analogy with modern tmRNA is obvious, and these could result from an ancient molecule of that type that lost its ability to act as a cleavable intron instead of losing its intermediate block. Indeed, when looking at the sizes, sequences, and positions of the introns in the secondary structure of modern tRNA, the introns correspond to the large RNA structure that replaces the anticodon stem‐loop in the tmRNA TLD . Therefore, the ancient proto‐tmRNA could be the common ancestor of both present‐day tmRNA and tRNA.…”

Self-Referential Encoding on Modules of Anticodon Pairs—Roots of the Biological Flow System

“…Our approach is centered on the elements proper to the encoding / decoding machinery -tRNAs and their anticodons, synthetases and amino acids, considering the strings of codons later developments, either enchained triplets derived from pre-encoded tRNAs [99][100][101][102][103] or exogenous strings that acquired the ability of being translated through evolutionary adjustments. Such strings and the decoding machinery would have coevolved with focus on e. g. speed while maintaining accuracy in translation, in a process that might have not preserved the details of the process of encoding.…”