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Molecular and Cellular Biology, August 2000, p. 5425-5432, Vol. 20, No. 15
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

In Vitro Properties of the Conserved Mammalian Protein hnRNP D Suggest a Role in Telomere Maintenance

Ashley Eversole1 and Nancy Maizels1,2,*

Departments of Molecular Biophysics and Biochemistry1 and Genetics,2 Yale University School of Medicine, New Haven, Connecticut 06520-8024

Received 20 December 1999/Returned for modification 3 February 2000/Accepted 5 May 2000

Mammalian chromosomes terminate with a 3' tail which consists of reiterations of the G-rich repeat, d(TTAGGG). The telomeric tail is the primer for replication by telomerase, and it may also invade telomeric duplex DNA to form terminal lariat structures, or T loops. Here we show that the ubiquitous and highly conserved mammalian protein hnRNP D interacts specifically with the G-rich strand of the telomeric repeat. A single gene encodes multiple isoforms of hnRNP D. All isoforms bind comparably to the G-rich strand, and certain isoforms can also bind tightly and specifically to the C-rich telomeric strand. G-rich telomeric sequences readily form structures stabilized by G-G pairing, which can interfere with telomere replication by telomerase. We show that hnRNP D binding to the G-rich strand destabilizes intrastrand G-G pairing and that hnRNP D interacts specifically with telomerase in human cell extracts. This biochemical analysis suggest that hnRNP D could function in vivo to destabilize structures formed by telomeric G-rich tails and facilitate their extension by telomerase.

* Corresponding author. Present address: Departments of Immunology and Biochemistry, University of Washington Medical School, Box 357650, 1959 NE Pacific St., Room H564 HSB, Seattle, WA 98195-7650. Phone: (206) 685-3956. Fax: (206) 543-1013. E-mail: maizels{at}u.washington.edu.

Molecular and Cellular Biology, August 2000, p. 5425-5432, Vol. 20, No. 15
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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