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

Hélène LaBranche, Sophie Dupuis, Yaacov Ben-David, Maria Rosa Bani, Raymund J. Wellinger, Benoit Chabot

Research output: Contribution to journalArticle

230 Citations (Scopus)

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 cells. Telomere elongation is carried out by telomerase, an RNA-dependent DNA polymerase which adds single-stranded TAGGGT repeats to the 3' ends of chromosomes. While proteins that associate with single-stranded telomeric repeats can influence tract lengths in yeast, 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 Al-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.

Original languageEnglish
Pages (from-to)199-202
Number of pages4
JournalNature Genetics
Volume19
Issue number2
DOIs
Publication statusPublished - 1998

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Telomerase
Telomere
Vertebrates
Mammalian Chromosomes
Heterogeneous-Nuclear Ribonucleoproteins
hnRNP A1
Cell Line
Chromosomal Instability
Chromosomes, Human, Pair 3
Cell Aging
RNA-Directed DNA Polymerase
DNA-Binding Proteins
Cell Survival
Yeasts
DNA

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase. / LaBranche, Hélène; Dupuis, Sophie; Ben-David, Yaacov; Bani, Maria Rosa; Wellinger, Raymund J.; Chabot, Benoit.

In: Nature Genetics, Vol. 19, No. 2, 1998, p. 199-202.

Research output: Contribution to journalArticle

LaBranche, H, Dupuis, S, Ben-David, Y, Bani, MR, Wellinger, RJ & Chabot, B 1998, 'Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase', Nature Genetics, vol. 19, no. 2, pp. 199-202. https://doi.org/10.1038/575
LaBranche, Hélène ; Dupuis, Sophie ; Ben-David, Yaacov ; Bani, Maria Rosa ; Wellinger, Raymund J. ; Chabot, Benoit. / Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase. In: Nature Genetics. 1998 ; Vol. 19, No. 2. pp. 199-202.
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