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RNA editing is a molecular clock in unmodified human cells
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RNA editing is a molecular clock in unmodified human cells
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Paper
RNA editing is a molecular clock in unmodified human cells
2024
Overview
Despite major advances in spatial RNA sequencing, the ability to extract temporal information in RNA sequencing experiments is still limited. Here, we describe Transcriptome Timestamping (T2), a system which harnesses naturally occurring A-to-I editing of RNA transcripts in unmodified human cells to infer transcriptional history. T2 provides age estimates for individual RNA transcripts, and serves as an endogenous molecular recorder, differentiating between complex transcriptional programs. We show that T2 can identify transient and transitional transcriptional programs in primary differentiating monocytes that are not apparent from gene expression analysis alone, including a regulatory module in the monocyte-to-macrophage transition that, to our knowledge, has not yet been described in humans. Finally, we show that T2 can also be applied to single cell data, allowing us to identify transcriptional programs in heterogeneous populations, such as asynchronously dividing cells. T2 is a scalable approach to temporal transcriptomics that can be applied to track the activity of thousands of genes in unmodified, primary human cells and tissues, with no genetic engineering.Competing Interest StatementA.G., J.B., A.W., D.M., G.Y. and S.G.R. are listed as inventors on UK patent application GB2400892.2. A.P.C. is a cofounder of Caeruleus Genomics Ltd and is an inventor on several patents related to sequencing technologies filed by Oxford University Innovations.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
