PT - JOURNAL ARTICLE AU - Samuel G. Rodriques AU - Linlin M. Chen AU - Sophia Liu AU - Ellen D. Zhong AU - Joseph R. Scherrer AU - Edward S. Boyden AU - Fei Chen TI - Recording the age of RNA with deamination AID - 10.1101/2020.02.08.939983 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.02.08.939983 4099 - http://biorxiv.org/content/early/2020/02/10/2020.02.08.939983.short 4100 - http://biorxiv.org/content/early/2020/02/10/2020.02.08.939983.full AB - Transcriptional programs implemented by cells often consist of complex temporal features, but current approaches to single-cell RNA sequencing only provide limited information about the dynamics of gene expression. Here, we present RNA timestamps, a method for inferring the age of individual RNAs in a sequencing-based readout by leveraging RNA editing. Timestamped RNAs include a RNA reporter motif that accumulates A to I edits over time, allowing the age of the RNA to be inferred with hour-scale accuracy. By combining observations of multiple timestamped RNAs driven by the same promoter, we are able to infer when in the past the promoter was active. We demonstrate that the system can infer the presence and timing of multiple past transcriptional events, with no prior knowledge. Finally, we apply this method to cluster single cells according to the times at which a particular transcriptional program was activated. RNA timestamps thus suggest a new approach for incorporating temporal information into RNA sequencing workflows.