This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gromak, N. Articles by Proudfoot, N. J. Search for Related Content PubMed PubMed Citation Articles by Gromak, N. Articles by Proudfoot, N. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2006, p. 3986-3996, Vol. 26, No. 10
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.10.3986-3996.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Pause Sites Promote Transcriptional Termination of Mammalian RNA Polymerase II

Natalia Gromak, Steven West, and Nick J. Proudfoot^*

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom

Received 25 November 2005/ Returned for modification 4 January 2006/ Accepted 2 March 2006

Polymerase II (Pol II) transcriptional termination depends on two independent genetic elements: poly(A) signals and downstream terminator sequences. The latter may either promote cotranscriptional RNA cleavage or pause elongating Pol II. We demonstrate that the previously characterized MAZ₄ pause element promotes Pol II termination downstream of a poly(A) signal, dependent on both the proximity of the pause site and poly(A) signal and the strength of the poly(A) signal. The 5'3' exonuclease Xrn2 facilitates this pause-dependent termination by degrading the 3' product of poly(A) site cleavage. The human ß-actin gene also possesses poly(A) site proximal pause sequences, which like MAZ₄ are G rich and promote transcriptional termination. Xrn2 depletion causes an increase in both steady-state RNA and Pol II levels downstream of the ß-actin poly(A) site. Taken together, we provide new insights into the mechanism of pause site-mediated termination and establish a general role for the 5'3' exonuclease Xrn2 in Pol II termination.

N.G. and S.W. are joint first authors.

This article has been cited by other articles:

• Respuela, P., Ferella, M., Rada-Iglesias, A., Aslund, L. (2008). Histone Acetylation and Methylation at Sites Initiating Divergent Polycistronic Transcription in Trypanosoma cruzi. J. Biol. Chem. 283: 15884-15892 [Abstract] [Full Text]  
• El Hage, A., Koper, M., Kufel, J., Tollervey, D. (2008). Efficient termination of transcription by RNA polymerase I requires the 5' exonuclease Rat1 in yeast. Genes Dev. 22: 1069-1081 [Abstract] [Full Text]  
• Greive, S. J., Weitzel, S. E., Goodarzi, J. P., Main, L. J., Pasman, Z., von Hippel, P. H. (2008). Monitoring RNA transcription in real time by using surface plasmon resonance. Proc. Natl. Acad. Sci. USA 105: 3315-3320 [Abstract] [Full Text]  
• West, S., Proudfoot, N. J. (2008). Human Pcf11 enhances degradation of RNA polymerase II-associated nascent RNA and transcriptional termination. Nucleic Acids Res 36: 905-914 [Abstract] [Full Text]  
• Kaneko, S., Chu, C., Shatkin, A. J., Manley, J. L. (2007). Human capping enzyme promotes formation of transcriptional R loops in vitro. Proc. Natl. Acad. Sci. USA 104: 17620-17625 [Abstract] [Full Text]  
• Boireau, S., Maiuri, P., Basyuk, E., de la Mata, M., Knezevich, A., Pradet-Balade, B., Backer, V., Kornblihtt, A., Marcello, A., Bertrand, E. (2007). The transcriptional cycle of HIV-1 in real-time and live cells. J. Cell Biol. 179: 291-304 [Abstract] [Full Text]  
• Kininis, M., Chen, B. S., Diehl, A. G., Isaacs, G. D., Zhang, T., Siepel, A. C., Clark, A. G., Kraus, W. L. (2007). Genomic Analyses of Transcription Factor Binding, Histone Acetylation, and Gene Expression Reveal Mechanistically Distinct Classes of Estrogen-Regulated Promoters. Mol. Cell. Biol. 27: 5090-5104 [Abstract] [Full Text]  
• Kaneko, S., Rozenblatt-Rosen, O., Meyerson, M., Manley, J. L. (2007). The multifunctional protein p54nrb/PSF recruits the exonuclease XRN2 to facilitate pre-mRNA 3' processing and transcription termination. Genes Dev. 21: 1779-1789 [Abstract] [Full Text]  
• Dalziel, M., Nunes, N. M., Furger, A. (2007). Two G-Rich Regulatory Elements Located Adjacent to and 440 Nucleotides Downstream of the Core Poly(A) Site of the Intronless Melanocortin Receptor 1 Gene Are Critical for Efficient 3' End Processing. Mol. Cell. Biol. 27: 1568-1580 [Abstract] [Full Text]