Genome Expansion by tRNA +1 Frameshifting at Quadruplet Codons. Issue 8 (30th April 2022)

• Record Type: Journal Article
• Authors: Gamper, Howard; Masuda, Isao; Hou, Ya-Ming
• Is Part Of: Journal of molecular biology. Volume 434:Issue 8(2022)
• Publication Date: 2022-04-30
• Subjects: SufB2 tRNA -- ProM tRNA -- ProL tRNA -- m1G37-tRNA -- mcmo5U34-tRNA; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2021.167440
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: Quadruplet decoding requires a +1-frameshifting event of the quadruplet-reading tRNA. No +1 frameshifting occurs in the ribosomal A site. The ribosome permits +1 frameshifting during translocation and P-site occupancy. Abstract: Inducing tRNA +1 frameshifting to read a quadruplet codon has the potential to incorporate a non-canonical amino acid (ncAA) into the polypeptide chain. While this strategy is attractive for genome expansion in biotechnology and bioengineering endeavors, improving the yield is hampered by a lack of understanding of where the shift can occur in an elongation cycle of protein synthesis. Lacking a clear answer to this question, current efforts have focused on designing +1-frameshifting tRNAs with an extra nucleotide inserted to the anticodon loop for pairing with a quadruplet codon in the aminoacyl-tRNA binding (A) site of the ribosome. However, the designed and evolved +1-frameshifting tRNAs vary broadly in achieving successful genome expansion. Here we summarize recent work on +1-frameshifting tRNAs. We suggest that, rather than engineering the quadruplet anticodon-codon pairing scheme at the ribosome A site, efforts should be made to engineer the pairing scheme at steps after the A site, including the step of the subsequent translocation and the step that stabilizes the pairing scheme in the +1-frame in the peptidyl-tRNA binding (P) site.