The antisense transcriptomes of human cells

Abstract

Transcription in mammalian cells can be assessed at a genome-wide level, but it has been difficult to reliably determine whether individual transcripts are derived from the plus or minus strands of chromosomes. This distinction can be critical for understanding the relationship between known transcripts (sense) and the complementary antisense transcripts that may regulate them. Here, we describe a technique that can be used to (i) identify the DNA strand of origin for any particular RNA transcript, and (ii) quantify the number of sense and antisense transcripts from expressed genes at a global level. We examined five different human cell types and in each case found evidence for antisense transcripts in 2900 to 6400 human genes. The distribution of antisense transcripts was distinct from that of sense transcripts, was nonrandom across the genome, and differed among cell types. Antisense transcripts thus appear to be a pervasive feature of human cells, which suggests that they are a fundamental component of gene regulation.

Fig. 1

ASSAGE tag densities in PBMC. The density of distinct sense and antisense tags in the indicated regions were normalized to the overall genome tag density. The promoter and terminator regions were defined as the 1 kb of sequence that was upstream or downstream, respectively, of the transcript start and end sites.

Fig. 2

Tag distribution in the indicated S (A) and AS (B) genes in PBMC.

Fig. 2

Tag distribution in the indicated S (A) and AS (B) genes in PBMC.