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Global Analysis of Short RNAs Reveals Widespread Promoter-Proximal Stalling and Arrest of Pol II in Drosophila

Science  15 Jan 2010:
Vol. 327, Issue 5963, pp. 335-338
DOI: 10.1126/science.1181421

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To Stall or Not to Stall

Recent studies in mammals and Drosophila have shown that RNA polymerase II frequently stalls shortly after initiating messenger RNA synthesis and that this stalling is important for proper expression of genes. Although several protein factors that affect polymerase stalling are known, the role of DNA sequence in this process has remained unclear. Now Nechaev et al. (p. 335, published online 10 December) report that the initially transcribed sequences of many genes contain a signal that works like a stop sign for the elongating polymerase. Expression of genes may thus be regulated by a combination of a DNA signal that induces promoter-proximal stalling and protein factors that alter its duration.

Abstract

Emerging evidence indicates that gene expression in higher organisms is regulated by RNA polymerase II stalling during early transcription elongation. To probe the mechanisms responsible for this regulation, we developed methods to isolate and characterize short RNAs derived from stalled RNA polymerase II in Drosophila cells. Significant levels of these short RNAs were generated from more than one-third of all genes, indicating that promoter-proximal stalling is a general feature of early polymerase elongation. Nucleotide composition of the initially transcribed sequence played an important role in promoting transcriptional stalling by rendering polymerase elongation complexes highly susceptible to backtracking and arrest. These results indicate that the intrinsic efficiency of early elongation can greatly affect gene expression.

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