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Schwalb, Björn; Michel, Margaux; Zacher, Benedikt; Frühauf, Katja; Demel, Carina; Tresch, Achim; Gagneur, Julien; Cramer, Patrick (2016): TT-seq maps the human transient transcriptome. In: Science, Vol. 352, No. 6290: pp. 1225-1228
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Abstract

Pervasive transcription of the genome produces both stable and transient RNAs. We developed transient transcriptome sequencing (TT-seq), a protocol that uniformly maps the entire range of RNA-producing units and estimates rates of RNA synthesis and degradation. Application of TT-seq to human K562 cells recovers stable messenger RNAs and long intergenic noncoding RNAs and additionally maps transient enhancer, antisense, and promoter-associated RNAs. TT-seq analysis shows that enhancer RNAs are short-lived and lack U1 motifs and secondary structure. TT-seq also maps transient RNA downstream of polyadenylation sites and uncovers sites of transcription termination;we found, on average, four transcription termination sites, distributed in a window with a median width of similar to 3300 base pairs. Termination sites coincide with a DNA motif associated with pausing of RNA polymerase before its release from the genome.