Prebiotic Assembly of Cloverleaf tRNA, Its Aminoacylation and the Origin of Coding, Inferred from Acceptor Stem Coding-Triplets.

tRNA is a key component in life's most fundamental process, the translation of the instructions contained in mRNA into proteins. Its role had to be executed as soon as the earliest translation emerged, but the questions of the prebiotic tRNA materialization, aminoacylation, and the origin of the coding triplets it carries are still open. Here, these questions are addressed by utilizing a distinct pattern of coding triplets highly conserved in the acceptor stems from the modern bacterial tRNAs of five early-emerging amino acids. Self-assembly of several copies of a short RNA oligonucleotide that carries a related pattern of coding triplets, via a simple and statistically feasible process, is suggested to result in a proto-tRNA model highly compatible with the cloverleaf secondary structure of the modern tRNA. Furthermore, these stem coding triplets evoke the possibility that they were involved in self-aminoacylation of proto-tRNAs prior to the emergence of the earliest synthetases, a process proposed to underlie the formation of the genetic code. Being capable of autonomous materialization and of self-aminoacylation, this verifiable model of the proto-tRNA advent adds principal components to an initial set of molecules and processes that may have led, exclusively through natural means, to the emergence of life.

Life is translation.

Evolutionary origin of translation represents one of the key questions that Carl Woese addressed in his work. Here we give a personal account of his results in this area and the effect they have had on the field.

Proteome-wide analysis reveals clues of complementary interactions between mRNAs and their cognate proteins as the physicochemical foundation of the genetic code.

Despite more than 50 years of effort, the origin of the genetic code remains enigmatic. Among different theories, the stereochemical hypothesis suggests that the code evolved as a consequence of direct interactions between amino acids and appropriate bases. If indeed true, such physicochemical foundation of the mRNA/protein relationship could also potentially lead to novel principles of protein-mRNA interactions in general. Inspired by this promise, we have recently explored the connection between the physicochemical properties of mRNAs and their cognate proteins at the proteome level. Using experimentally and computationally derived measures of solubility of amino acids in aqueous solutions of pyrimidine analogs together with knowledge-based interaction preferences of amino acids for different nucleobases, we have revealed a statistically significant matching between the composition of mRNA coding sequences and the base-binding preferences of their cognate protein sequences. Our findings provide strong support for the stereochemical hypothesis of genetic code's origin and suggest the possibility of direct complementary interactions between mRNAs and cognate proteins even in present-day cells.

Coding From Binding? Molecular Interactions at the Heart of Translation.

The mechanism and the evolution of DNA replication and transcription, the key elements of the central dogma of biology, are fundamentally well explained by the physicochemical complementarity between strands of nucleic acids. However, the determinants that have shaped the third part of the dogma-the process of biological translation and the universal genetic code-remain unclear. We review and seek parallels between different proposals that view the evolution of translation through the prism of weak, noncovalent interactions between biological macromolecules. In particular, we focus on a recent proposal that there exists a hitherto unrecognized complementarity at the heart of biology, that between messenger RNA coding regions and the proteins that they encode, especially if the two are unstructured. Reflecting the idea that the genetic code evolved from intrinsic binding propensities between nucleotides and amino acids, this proposal promises to forge a link between the distant past and the present of biological systems.

Emergence of a "Cyclosome" in a Primitive Network Capable of Building "Infinite" Proteins.

We argue for the existence of an RNA sequence, called the AL (for ALpha) sequence, which may have played a role at the origin of life; this role entailed the AL sequence helping generate the first peptide assemblies via a primitive network. These peptide assemblies included "infinite" proteins. The AL sequence was constructed on an economy principle as the smallest RNA ring having one representative of each codon's synonymy class and capable of adopting a non-functional but nevertheless evolutionarily stable hairpin form that resisted denaturation due to environmental changes in pH, hydration, temperature, etc. Long subsequences from the AL ring resemble sequences from tRNAs and 5S rRNAs of numerous species like the proteobacterium, Rhodobacter sphaeroides. Pentameric subsequences from the AL are present more frequently than expected in current genomes, in particular, in genes encoding some of the proteins associated with ribosomes like tRNA synthetases. Such relics may help explain the existence of universal sequences like exon/intron frontier regions, Shine-Dalgarno sequence (present in bacterial and archaeal mRNAs), CRISPR and mitochondrial loop sequences.