Genetic engineering

Transcriptional recorder

Nature 562, 380–385 (2018)

Microbial CRISPR–Cas systems can integrate short foreign DNA sequences into a host’s genome, recording a memory of infection for use in future immune responses. These acquired sequences, called spacers, are separated by direct repeats and constitute CRISPR arrays. Though acquisition of CRISPR spacers from RNA has been found in some marine organisms, it is not clear whether this mechanism can be expanded to other organisms. Schmidt et al. found that Cas1–Cas2 from Fusicatenibacter saccharivorans (FsRT–Cas1–Cas2) was able to capture and convert RNAs into DNA spacers in Escherichia coli. By sequencing the CRISPR arrays, they found that RNA-derived spacers captured by FsRT–Cas1–Cas2 were mainly from AT-rich regions at the ends of transcripts and were positively correlated to the cumulative transcript abundance. This method, termed Record-seq, enabled quantitative recording of transcriptome-wide alterations under oxidative and acid-stress-stimulated conditions. Notably, Record-seq succeeded in recording the historical transcriptional changes induced by transient paraquat exposure, whereas traditional RNA-seq failed due to the recovered transcriptional level after paraquat removal. This study provides a useful tool for molecular recording and paves a way for transcriptional lineage tracking.

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Correspondence to Yiyun Song.

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Song, Y. Transcriptional recorder. Nat Chem Biol 14, 1067 (2018). https://doi.org/10.1038/s41589-018-0174-5

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