Cell Cycle-dependent Usage of Transcriptional Start Sites
A NOVEL MECHANISM FOR REGULATION OF CYCLIN B1*
- From the Departments of ‡Pathology and Laboratory Medicine and §Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Abstract
Cyclin B1 mRNA is expressed temporally throughout the cell cycle with peak expression in G2and M phase. Both transcriptional and posttranscriptional controls are important for this cell cycle-dependent regulation of cyclin B1 mRNA. In this study, we observed that cyclin B1 has two major transcripts: (a) a constitutively expressed transcript, and (b) a cell cycle-regulated transcript expressed predominantly during G2-M phase. These different transcripts are due to alternative start sites. The constitutively expressed transcript starts 65 bases upstream from the cell cycle-regulated message. Changes in mRNA stability did not appear to control the expression of the cell cycle-specific transcript, but we were able to identify a 24-base pair region of the cyclin B1 promoter spanning the start site of the cell cycle-regulated transcript that was critical for its cell cycle-regulated promoter activity. This suggests that transcriptional regulation is responsible for controlling the presence of each message. The 24-base pair sequence required for cell cycle regulation was notable for containing the nucleotides GGCT repeated three times. The possibility that these two transcripts might be physiologically distinct was raised when the cell cycle-specific transcript was found to be translated more efficientlyin vitro than the constitutively expressed transcript. These results characterize a novel mechanism for the regulation of cyclin B1 throughout the cell cycle that is dependent upon the use of different transcriptional start sites.
Footnotes
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↵* This work was supported by United States Public Health Service Grant GM 47439 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵¶ To whom correspondence should be addressed: Dept. of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 269 John Morgan Building, 36th and Hamilton Walk, Philadelphia, PA 19104. Tel.: 215-898-8401; Fax: 215-573-4243.
- Abbreviations:
- bp
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base pair(s)
- PCR
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polymerase chain reaction.
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- Received April 28, 1998.
- Revision received August 25, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
