The natural history of transfer RNA and its interactions with the ribosome

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Transfer RNA (tRNA) is undoubtedly the most central and one of the oldest molecules of the cell. Without it genetics and coded protein synthesis are impossible. The crucial specificities responsible for the genetic code and accurate translation are by far entrusted to interactions between tRNA and translation proteins, fundamentally aminoacyl-tRNA synthetase (aaRS) enzymes and elongation factor (EF) switches (Yadavalli and Ibba, 2012). Discrimination mediated by aaRSs and EFs against misincorporated tRNA and amino acids is at least 20 times more stringent than ribosomal recognition, editing, and other proofreading mechanisms (Reynolds et al., 2010). The fact that crucial genetic code specificities in highly selective interactions with protein enzymes do not involve the ribosomal ribonucleoprotein biosynthetic machinery challenges the "replicators first" origin of life scenario of an ancient RNA world (Caetano-Anollès and Seufferheld, 2013). It also highlights the central functional, mechanistic, and evolutionary roles of tRNA and its recognition determinants, which enable coevolution between nucleic acids and proteins. These coevolutionary relationships are compatible with a late origin of the ribosome in its mechanism and not in protein biosynthesis, which was inferred from the computational analysis of thousands of RNAs and proteomes (Harish and Caetano-Anollès, 2012). These analyses showed tight coevolution of ribosomal RNA (rRNA) and ribosomal proteins (r-proteins). While these relationships delimit molecular makeup when organisms use translation to negotiate growth and viability amidst environmental change, coevolution also constrains recruitment of the canonical L-shaped structure of the tRNA molecule into a multiplicity of modern functions. These new functions include the synthesis of antibiotics, bacterial cell wall peptidoglycans and tetrapyrroles, modification of bacterial membrane lipids, protein turnover, and the synthesis of other aminoacyl-tRNA molecules (Francklyn and Minajigi, 2010). Here we unfold coevolutionary relationships between tRNA substructures and translation proteins that embody crucial protein-nucleic acid interactions. We focus on a series of computational biology analyses of the structure and conformational diversity of tRNAs and their interacting proteins that provide information about the history of structural accretion of this "adaptor" molecule. Using this information, we place tRNA history within the framework of an evolutionary timeline of protein domain innovation, uncovering the natural history of tRNA within the context of the geological record.

Original languageEnglish (US)
Article number127
JournalFrontiers in Genetics
Issue numberMAY
StatePublished - 2014


  • Non-coding RNA
  • Origin of life
  • Phylogenetic analysis
  • Ribosome
  • Sequence
  • Structure
  • Translation

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)


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