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 Peterson, M. L. Articles by Davis, F. Search for Related Content PubMed PubMed Citation Articles by Peterson, M. L. Articles by Davis, F.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2002, p. 5606-5615, Vol. 22, No. 15
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.15.5606-5615.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

An RNA Polymerase Pause Site Is Associated with the Immunoglobulin µs Poly(A) Site

Department of Pathology and Laboratory Medicine, Department of Microbiology, Immunology, and Molecular Genetics, and the Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40536

Received 24 January 2002/ Returned for modification 8 March 2002/ Accepted 3 May 2002

Immunoglobulin µ alternative RNA processing is regulated during B-cell maturation and requires balanced efficiencies of the competing splice (µm) and cleavage-polyadenylation (µs) reactions. When we deleted sequences 50 to 200 nucleotides beyond the µs poly(A) site, the µs/µm mRNA ratio decreased three- to eightfold in B, plasma, and nonlymphoid cells. The activity could not be localized to a smaller fragment but did function in heterologous contexts. Our data suggest that this region contains an RNA polymerase II pause site that enhances the use of the µs poly(A) site. First, known pause sites replaced the activity of the deleted fragment. Second, the µ fragment, when placed between tandem poly(A) sites, enhanced the use of the upstream poly(A) site. Finally, nuclear run-ons detected an increase in RNA polymerase loading just downstream from the µs poly(A) site, even when the poly(A) site was inactivated. When this µ fragment and another pause site were inserted 1 kb downstream from the µs poly(A) site, they no longer affected the mRNA expression ratio, suggesting that pause sites affect poly(A) site use over a limited distance. Fragments from the immunoglobulin A gene were also found to have RNA polymerase pause site activity.

This article has been cited by other articles:

• Sanchez, G., Bittencourt, D., Laud, K., Barbier, J., Delattre, O., Auboeuf, D., Dutertre, M. (2008). Alteration of cyclin D1 transcript elongation by a mutated transcription factor up-regulates the oncogenic D1b splice isoform in cancer. Proc. Natl. Acad. Sci. USA 105: 6004-6009 [Abstract] [Full Text]  
• Ke, J., Gururajan, M., Kumar, A., Simmons, A., Turcios, L., Chelvarajan, R. L., Cohen, D. M., Wiest, D. L., Monroe, J. G., Bondada, S. (2006). The Role of MAPKs in B Cell Receptor-induced Down-regulation of Egr-1 in Immature B Lymphoma Cells. J. Biol. Chem. 281: 39806-39818 [Abstract] [Full Text]  
• Peterson, M. L., Bingham, G. L., Cowan, C. (2006). Multiple features contribute to the use of the immunoglobulin m secretion-specific poly(a) signal but are not required for developmental regulation.. Mol. Cell. Biol. 26: 6762-6771 [Abstract] [Full Text]  
• Nag, A., Narsinh, K., Kazerouninia, A., Martinson, H. G. (2006). The conserved AAUAAA hexamer of the poly(A) signal can act alone to trigger a stable decrease in RNA polymerase II transcription velocity. RNA 12: 1534-1544 [Abstract] [Full Text]  
• WEST, S., ZARET, K., PROUDFOOT, N. J. (2006). Transcriptional termination sequences in the mouse serum albumin gene.. RNA 12: 655-665 [Abstract] [Full Text]  
• Plant, K. E., Dye, M. J., Lafaille, C., Proudfoot, N. J. (2005). Strong Polyadenylation and Weak Pausing Combine To Cause Efficient Termination of Transcription in the Human G{gamma}-Globin Gene. Mol. Cell. Biol. 25: 3276-3285 [Abstract] [Full Text]  
• KORNBLIHTT, A. R., DE LA MATA, M., FEDEDA, J. P., MUNOZ, M. J., NOGUES, G. (2004). Multiple links between transcription and splicing. RNA 10: 1489-1498 [Abstract] [Full Text]  
• Robson-Dixon, N. D., Garcia-Blanco, M. A. (2004). MAZ Elements Alter Transcription Elongation and Silencing of the Fibroblast Growth Factor Receptor 2 Exon IIIb. J. Biol. Chem. 279: 29075-29084 [Abstract] [Full Text]  
• Park, N. J., Tsao, D. C., Martinson, H. G. (2004). The Two Steps of Poly(A)-Dependent Termination, Pausing and Release, Can Be Uncoupled by Truncation of the RNA Polymerase II Carboxyl-Terminal Repeat Domain. Mol. Cell. Biol. 24: 4092-4103 [Abstract] [Full Text]  
• Cui, Y., Denis, C. L. (2003). In Vivo Evidence that Defects in the Transcriptional Elongation Factors RPB2, TFIIS, and SPT5 Enhance Upstream Poly(A) Site Utilization. Mol. Cell. Biol. 23: 7887-7901 [Abstract] [Full Text]  
• Orozco, I. J., Kim, S. J., Martinson, H. G. (2002). The Poly(A) Signal, without the Assistance of Any Downstream Element, Directs RNA Polymerase II to Pause in Vivo and Then to Release Stochastically from the Template. J. Biol. Chem. 277: 42899-42911 [Abstract] [Full Text]