The concept of RNA-assisted protein folding: the role of tRNA

The concept of nucleic acid-assisted protein folding (nucleic acid chaperons) was first published in 2005 [1], when it was suggested that mRNAs participate in the formation of the tertiary structure of their coded proteins; this function is in addition to the well-recognized determination of the amino acid sequence of the proteins, as described in Nirenberg's Genetic Code. Messenger RNAs often have a tertiary structure that provides spatial information for protein folding, i.e. they are nucleic acid chaperons [2]. Nucleic acid-assisted protein folding requires that mRNA and coded peptides remain in contact with each other, even after the polymerization of the amino acids during translation. The original model described RNA-assisted protein folding, but the role of tRNA was not properly elucidated.The role of the t-RNAs is to "translate" between mRNA and the encoded peptide, which means that tRNAs recognizes the codons in mRNA and arrange the amino acids in the order of the codons for polymerization by the protein synthetase. This function could be performed by a much smaller oligonucleotide containing only four nucleotides, three for the anticodon and one for binding the corresponding amino acid. However tRNAs are much larger, about 76 nucleotides in length.The abundance of tRNA is another mystery. The 64 different codons require 64 different "mediators", but there are many more. There are, for example, 359 different cytoplasmic tRNAs in human cells, and many more when genomic variants are included. The generous size and lavish redundancy suggest that the function of tRNAs is far more complex than the passive connecting of codons with their amino acids that has been recognized to date.The aim of this work is to identify additional functions for tRNAs in translation, and to explain their involvement and role in nucleic acid-mediated protein folding.The existence of tRNA was hypothesized by Francis Crick in 1956 [3,4] to explain the transfer of information (translatio