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Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase

Nature Genetics volume 19, pages 199–202 (1998)Cite this article

Abstract

Telomeric DNA of mammalian chromosomes consists of several kilobase-pairs of tandemly repeated sequences with a terminal 3´ overhang in single-stranded form. Maintaining the integrity of these repeats is essential for cell survival; telomere attrition is associated with chromosome instability and cell senescence, whereas stabilization of telomere length correlates with the immortalization of somatic cells1. Telomere elongation is carried out by telomerase, an RNA-dependent DNA polymerase which adds single-stranded TAGGGT repeats to the 3´ ends of chromosomes1. While proteins that associate with single-stranded telomeric repeats can influence tract lengths in yeast2,3, equivalent factors have not yet been identified in vertebrates. Here, it is shown that the heterogeneous nuclear ribonucleoprotein A1 participates in telomere biogenesis. A mouse cell line deficient in A1 expression harbours telomeres that are shorter than those of a related cell line expressing normal levels of A1. Restoring A1 expression in A1-deficient cells increases telomere length. Telomere elongation is also observed upon introduction of exogenous UP1, the amino-terminal fragment of A1. While both A1 and UP1 bind to vertebrate single-stranded telomeric repeats directly and with specificity in vitro, only UP1 can recover telomerase activity from a cell lysate. These findings establish A1/UP1 as the first single-stranded DNA binding protein involved in mammalian telomere biogenesis and suggest possible mechanisms by which UP1 may modulate telomere length.

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Figure 1: A1 expression affects telomere length.
Figure 2: UP1 promotes telomere elongation in mammalian cells.
Figure 3: UP1 binds directly and with specificity to single-stranded vertebrate telomeric repeats.
Figure 4: UP1 interacts with telomerase in vitro.

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Acknowledgements

We thank G. Dreyfuss for the anti-A1 antibody, S. Bacchetti for mutated oligonucleotides and A. Weiner and V. Zakian for comments on the manuscript. We thank J. Toutant for expert technical assistance, C. LeBel for constructing the GST-UP1 and GST-A1 vectors and F. Dallaire for the production of the GST-A1 protein. We also thank N.W. Kim, C. Harley and Geron Corporation for permitting the use and providing information on the TRAP assay. This work was supported by grants to B.C. and R.J.W. from the National Cancer Institute of Canada with funds from the Canadian Cancer Society and to Y. B.-D. from the Medical Research Council of Canada. S.D. is supported by a studentship from the F.C.A.R. Y.B.-D. is a Research Scholar, supported by the National Cancer Institute of Canada. B.C. and R.J.W. are Chercheurs-Boursiers Senior from the Fonds de la Recherche en Santé du Québec.

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Authors and Affiliations

  1. Département de Microbiologie et d'Infectiologie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada

    Hélène LaBranche, Sophie Dupuis, Raymund J. Wellinger & Benoit Chabot

  2. Sunnybrook Health Science Centre and Department of Medical Biophysics, University of Toronto, Toronto, M4N 3M5, Ontario, Canada

    Yaacov Ben-David & Maria-Rosa Bani

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  1. Hélène LaBranche
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  6. Benoit Chabot
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Correspondence to Benoit Chabot.

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LaBranche, H., Dupuis, S., Ben-David, Y. et al. Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase. Nat Genet 19, 199–202 (1998). https://doi.org/10.1038/575

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