Molecular Biology

Promoting Silence

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Science  27 Jul 2007:
Vol. 317, Issue 5837, pp. 427
DOI: 10.1126/science.317.5837.427d

RNA interference (RNAi) can modulate gene expression at the posttranscriptional stage by prompting the degradation of mRNA or blocking its translation into protein. The mRNA is targeted by homologous ~22-nt short interfering (si) RNAs. RNAi can also inhibit gene transcription itself, promoting the formation of silent heterochromatin in yeast, and evidence indicates that siRNAs act via the degradation of low-abundance nascent transcripts, rather than on the DNA. In human cells, siRNAs directed against promoter sequences can block gene transcription. Do these siRNAs act on the promoter DNA or, as in yeast, an RNA species? Han et al. analyze transcripts from the human EF1a promoter and find a low-abundance sense RNA that initiates ~230 bp upstream of the previously characterized promoter and appears to be a variant EF1a mRNA. Suppression of this variant reduces the ability of promoter-targeted siRNAs to induce transcriptional silencing and to enhance the formation of associated silent chromatin marks. Related results are seen for several other gene promoters in human cells, leading the authors to speculate that these promoter RNAs might function similarly in vivo. — GR

Proc. Natl. Acad. Sci. U.S.A. 104, 10.1073/pnas.0701635104 (2007).

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