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RNA biotechnology
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Start codon selection by ribosomes is a crucial regulatory step in translation that can produce distinct protein isoforms and levels. However, it is difficult to enhance translation in a start codon-selective manner without imposing changes to the mRNA sequence of interest being translated. Now, Jia et al. have addressed this issue by designing capped trans-RNAs that direct ribosomes to specific initiation sites on target mRNAs to promote their translation.
The trans-RNAs are small RNAs equipped with a 5′ cap that mimics the 5′ end of natural mRNAs. These trans-RNAs are designed to be complementary to regions upstream of the target start codon, and their 5′ cap structure facilitates ribosome access to the adjacent start codon. The team provided two in vivo examples of how trans-RNAs can be applied to regulate the expression of endogenous genes without altering mRNA levels.
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Song, Y. Programmable translation. Nat Chem Biol (2025). https://doi.org/10.1038/s41589-025-02115-8
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DOI: https://doi.org/10.1038/s41589-025-02115-8
