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Garbled messages and corrupted translations

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Abstract

Following transcription, genomic information begins a long journey toward translation of its nucleotide sequence into the amino acids of a protein. In eukaryotes, synthesized pre-mRNAs become processed to mature mRNAs by 5′-end capping, splicing, 3′-end cleavage and polyadenylation in the nucleus, before being scrutinized for premature stop codons. Each step requires high precision and control to ensure that an intact and readable message is exported to the cytoplasm before finally becoming translated. Two important aspects of these processes are accurately managed by ribonucleoprotein machineries—the spliceosome and the ribosome. Recently, several natural products targeting these macromolecular assemblies have been reported. For the first time in eukaryotes, these molecules allow chemical disruption and dissection of the sophisticated machinery that regulates post-transcriptional events. Beyond their great potential as bioprobes for investigating mRNA regulation and protein synthesis, these compounds also show promise in opening new therapeutic approaches.

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Figure 1
Figure 2: Recognition of sequences around the intron-exon borders by splicing factors.
Figure 3: Simplified summary of eukaryotic translation initiation.
Figure 4: The eukaryotic translation elongation cycle.

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  • 18 March 2010

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Acknowledgements

We thank J.O. Liu of the Johns Hopkins University School of Medicine for his support and for making an unpublished manuscript available to us.

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Schneider-Poetsch, T., Usui, T., Kaida, D. et al. Garbled messages and corrupted translations. Nat Chem Biol 6, 189–198 (2010). https://doi.org/10.1038/nchembio.326

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