Translation articles within Nature Chemistry

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• News & Views | 29 June 2023

  Establishing the fundamental rules for genetic code expansion

  Genetic code expansion beyond α-amino acids is a major challenge, in which stitching together non-natural building blocks within the ribosome is a critical barrier. Now, the molecular determinants for the efficient incorporation of non-natural amino acids into the ribosome have been unlocked, accelerating ribosomal synthesis.

  • Souvik Sinha
  • , Mohd Ahsan
  •  & Giulia Palermo

• Research Briefing | 19 June 2023

  Five mutually orthogonal aaRS–tRNA pairs for genetic code expansion

  Protein translation is the ultimate paradigm for sequence-defined polymer synthesis. To introduce non-canonical monomers into the genetic code of living organisms, pairs of biomolecules known as aminoacyl-tRNA synthetases (aaRSs) and transfer RNAs (tRNAs) are required. The discovery and engineering of five such pairs, that do not interfere with each other or the aaRS–tRNA pairs of a bacterial host, sets the stage for highly modified genetically encoded biopolymers.

• Article
  22 May 2023 | Open Access

  In vitro selection of macrocyclic peptide inhibitors containing cyclic γ^2,4-amino acids targeting the SARS-CoV-2 main protease

  In vitro screening of a ribosomally synthesized macrocyclic peptide library containing cyclic γ^2,4-amino acids (cγAA) afforded the discovery of potent inhibitors of the SARS-CoV-2 main protease (M^pro). A co-crystal structure revealed the contribution of this cγAA to M^pro binding and the proteolytic stability of these macrocycles.

  • Takashi Miura
  • , Tika R. Malla
  •  & Hiroaki Suga

• Article | 31 October 2022

  Insights into the ribosome function from the structures of non-arrested ribosome–nascent chain complexes

  Synthesis of peptidyl-tRNAs is challenging because there are no enzymes that can directly attach the desired peptide to tRNA. Now it has been shown that a chemoenzymatic approach based on native chemical ligation can be used for the semi-synthesis of peptidyl-tRNAs for structural/biochemical studies of arrested and non-arrested ribosome complexes.

  • Egor A. Syroegin
  • , Elena V. Aleksandrova
  •  & Yury S. Polikanov

• Article
  20 June 2022 | Open Access

  Photocaged 5′ cap analogues for optical control of mRNA translation in cells

  Analogues of mRNA 5′ caps containing a photo-cleavable group have now been developed. These so-called FlashCaps can be used for routine in vitro transcription to make long mRNAs containing a cap. In cells, the capped mRNAs are translationally muted; however, upon irradiation by light, the photo-cleavable group is removed without leaving any remaining modification and mRNA is then translated into the corresponding protein.

  • Nils Klöcker
  • , Florian P. Weissenboeck
  •  & Andrea Rentmeister

• Article
  14 October 2021 | Open Access

  Interactions between nascent proteins and the ribosome surface inhibit co-translational folding

  During polypeptide biosynthesis, a strong interaction can occur between a segment of an emerged, disordered nascent protein and the ribosomal surface. Now, it has been shown that competition between this ribosomal binding and the folding energetics of an immunoglobulin-like domain modulates the mechanism of co-translational folding.

  • Anaïs M. E. Cassaignau
  • , Tomasz Włodarski
  •  & John Christodoulou

• Article | 23 August 2021

  A 68-codon genetic code to incorporate four distinct non-canonical amino acids enabled by automated orthogonal mRNA design

  Non-canonical amino acids can be incorporated into proteins through translation of orthogonal mRNAs. Now, automating the design of orthogonal mRNAs—which are more selectively and efficiently translated—in combination with compact orthogonal aminoacyl-tRNA synthetase/tRNA expression systems, enables the incorporation of four distinct non-canonical monomers via a 68-codon genetic code.

  • Daniel L. Dunkelmann
  • , Sebastian B. Oehm
  •  & Jason W. Chin

• Article | 24 August 2020

  Ribosomal synthesis and de novo discovery of bioactive foldamer peptides containing cyclic β-amino acids

  Cyclic β-amino acids can add useful properties to peptides, such as inducing turn structures or providing resistance to proteases. To harness these properties up to ten consecutive cyclic β-amino acids have now been ribosomally incorporated via genetic code reprogramming into a foldamer peptide library that has been screened for potent binders against a protein target, human factor XIIa.

  • Takayuki Katoh
  • , Toru Sengoku
  •  & Hiroaki Suga

• Article | 18 July 2010

  A polyhedron made of tRNAs

  Whereas synthetic DNA nanostructures are widely studied, the use of RNA as a structural building block is much less common. Now, it has been shown that tRNA molecules can be designed to assemble into a rigid and thermally stable square antiprism structure that may prove useful for delivery applications inside cells.

  • Isil Severcan
  • , Cody Geary
  •  & Luc Jaeger