Mechanism of PTC readthrough strategies (IMAGE)

Science China Press

Mechanism of PTC readthrough strategies

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(A) Suppressor tRNA readthrough strategy. Natural tRNAs with engineered anticodons are charged with canonical amino acids to enable readthrough of the premature termination codon (PTC). (B) Unnatural aaRS-tRNA pairs readthrough strategy. Unnatural aaRS-tRNA pairs facilitate readthrough of the PTCs by incorporation of unnatural amino acids. (C) Aminoglycosides readthrough strategy. Aminoglycosides disrupt the ribosome decoding center, leading to misincorporation of the near-cognate aminoacyl-tRNA and subsequent readthrough of the PTCs. (D) Pseudouridylation of PTCs strategy. Targeted pseudouridylation of uridine in PTCs suppresses PTC-induced translation termination. (E) Antisense oligonucleotides (ASO) strategy. ASOs can be designed to modulate RNA splicing, resulting in the PTC-containing exon skipping. (F) Gene editing strategy. Adenine base editors (ABEs) convert targeted A·T base pairs to G·C base pairs, thereby altering PTCs to normal coding sequences.

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