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Molecular and Cellular Biology, September 2001, p. 6151-6160, Vol. 21, No. 18
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.18.6151-6160.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Functional Multimerization of the Human Telomerase Reverse Transcriptase

Tara L. Beattie,1,* Wen Zhou,2 Murray O. Robinson,2 and Lea Harrington1,*

Ontario Cancer Institute/Amgen Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada,1 and Amgen, Inc., Thousand Oaks, California2

Received 22 March 2001/Returned for modification 30 April 2001/Accepted 2 July 2001

The telomerase enzyme exists as a large complex (~1,000 kDa) in mammals and at minimum is composed of the telomerase RNA and the catalytic subunit telomerase reverse transcriptase (TERT). In Saccharomyces cerevisiae, telomerase appears to function as an interdependent dimer or multimer in vivo (J. Prescott and E. H. Blackburn, Genes Dev. 11:2790-2800, 1997). However, the requirements for multimerization are not known, and it remained unclear whether telomerase exists as a multimer in other organisms. We show here that human TERT (hTERT) forms a functional multimer in a rabbit reticulocyte lysate reconstitution assay and in human cell extracts. Two separate, catalytically inactive TERT proteins can complement each other in trans to reconstitute catalytic activity. This complementation requires the amino terminus of one hTERT and the reverse transcriptase and C-terminal domains of the second hTERT. The telomerase RNA must associate with only the latter hTERT for reconstitution of telomerase activity to occur. Multimerization of telomerase also facilitates the recognition and elongation of substrates in vitro and in vivo. These data suggest that the catalytic core of human telomerase may exist as a functionally cooperative dimer or multimer in vivo.

* Corresponding author. Mailing address for Tara L. Beattie: Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada T2N 4N1. Phone: (403) 220-8328. Fax: (403) 283-8727. E-mail: tbeattie{at}ucalgary.ca. Mailing address for Lea Harrington: Ontario Cancer Institute/Amgen Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2C1. Phone: (416) 204-2231. Fax: (416) 204-2277. E-mail: leah{at}uhnres.utoronto.ca.

Molecular and Cellular Biology, September 2001, p. 6151-6160, Vol. 21, No. 18
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.18.6151-6160.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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