Transcription Changes Direction

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Science  19 Dec 2008:
Vol. 322, Issue 5909, pp. 1753
DOI: 10.1126/science.322.5909.1753n

RNA polymerase II (RNAPII) is generally thought to generate mature messenger RNAs by elongation of transcripts that initiate in a single direction from the transcription start site (TSS). Results from four independent groups (see the Perspective by Buratowski) show that transcriptional activity at mammalian promoters is far more complex than this. In a study of mouse and human cells, Seila et al. (p. 1849) identified short bidirectionally transcribed RNAs that flank active promoters, with sense and anti-sense RNAs peaking at 50 nucleotides downstream, and 250 upstream of the TSS, respectively. Both sense and antisense peaks coincided with hallmarks of transcription initiation. Core et al. (p. 1845) mapped the position, abundance, and orientation of transcriptionally engaged RNA polymerases in human fibroblasts at a genome-wide level. Promoter-proximal polymerase was detected on about 30% of human genes, and most active promoters produced short antisense transcripts in both directions from a site upstream of the TSS, although elongation occurred in only one direction. Using a method to limit RNA degradation in human HeLa cells, Preker et al. (p. 1851) identified what may represent yet another class of small RNAs, which are short-lived and are produced 0.5 to 2.5 kilobases upstream of the TSS by bidirectional transcription at active promoters. Finally, He et al. (p. 1855) developed a method for quantifying the sense and antisense transcripts derived from all expressed genes. Analysis of five human cell lines revealed that antisense transcripts are abundant, nonrandomly distributed across the genome, and differ according to cell type.

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