Ribosome-Free Translation

• Applicant: Professor Dr. Clemens Richert
• Subject Area: Biological and Biomimetic Chemistry
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 516444519

The synthesis of peptides, instructed by nucleic acids, is a pivotal process for life as we know it. The biosynthesis of proteins occurs via translation. Translation is an RNA-directed process, involving an mRNA, tRNAs, and ribosomes with an RNA core, but it is difficult to see how so complex a machinery could have emerged from random sequences. There must have been a simpler form of RNA-induced peptide synthesis that then evolved into an ever more sophisticated system. One proposal is that this simpler form may have involved peptido RNA, i.e. phosphoramidate-linked species that form spontaneously from nucleotides and amino acids. In our current study, we learned that nanoscale RNA structures can favor the formation of both peptido RNAs and free peptides. Additionally, we established the first ribosome-free form of translation. Depending on the RNA template, different amino acids are incorporated at the C-terminus of a growing peptido RNA in the absence of ribosomes or enzymes. Extending this form of translation to longer sequences requires spatial control over template, primer and tRNA species. To accomplish this, we will prepare new aminoacylate adaptor molecules and employ new template constructs. We will test constructs inspired by the positioning capabilities known from nucleic acid nanotechnology and from nonribosomal peptide synthesis. The combination of positional control and dynamic, sequence-specific interactions is expected to provide insights into one of the most difficult problems in the study of the origin of life and on template-directed, encoded reaction in general.

• DFG Programme: Research Grants