hnRNP A1 associates with telomere ends and stimulates telomerase activity

Qing-Shuo Zhang, Lisa Manche, Rui Ming Xu, Adrian R. Krainer

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Telomerase is a ribonucleoprotein enzyme complex that reverse-transcribes an integral RNA template to add short DNA repeats to the 3′-ends of telomeres. G-quadruplex structure in a DNA substrate can block its extension by telomerase. We have found that hnRNP A1 - which was previously implicated in telomere length regulation - binds to both single-stranded and structured human telomeric repeats, and in the latter case, it disrupts their higher-order structure. Using an in vitro telomerase assay, we observed that depletion of hnRNP A/B proteins from 293 human embryonic kidney cell extracts dramatically reduced telomerase activity, which was fully recovered upon addition of purified recombinant hnRNP A1. This finding suggests that hnRNP A1 functions as an auxiliary, if not essential, factor of telomerase holoenzyme. We further show, using chromatin immunoprecipitation, that hnRNP A1 associates with human telomeres in vivo. We propose that hnRNP A1 stimulates telomere elongation through unwinding of a G-quadruplex or G-G hairpin structure formed at each translocation step.

Original languageEnglish (US)
Pages (from-to)1116-1128
Number of pages13
JournalRNA
Volume12
Issue number6
DOIs
StatePublished - Jun 2006

Fingerprint

Telomerase
Telomere
G-Quadruplexes
Heterogeneous-Nuclear Ribonucleoprotein Group A-B
Holoenzymes
Ribonucleoproteins
Chromatin Immunoprecipitation
DNA
Cell Extracts
hnRNP A1
RNA
Kidney
Enzymes

Keywords

  • G-quadruplex
  • hnRNP A1
  • Processivity
  • Telomerase
  • Telomere

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology

Cite this

Zhang, Q-S., Manche, L., Xu, R. M., & Krainer, A. R. (2006). hnRNP A1 associates with telomere ends and stimulates telomerase activity. RNA, 12(6), 1116-1128. https://doi.org/10.1261/rna.58806

hnRNP A1 associates with telomere ends and stimulates telomerase activity. / Zhang, Qing-Shuo; Manche, Lisa; Xu, Rui Ming; Krainer, Adrian R.

In: RNA, Vol. 12, No. 6, 06.2006, p. 1116-1128.

Research output: Contribution to journalArticle

Zhang, Q-S, Manche, L, Xu, RM & Krainer, AR 2006, 'hnRNP A1 associates with telomere ends and stimulates telomerase activity', RNA, vol. 12, no. 6, pp. 1116-1128. https://doi.org/10.1261/rna.58806
Zhang, Qing-Shuo ; Manche, Lisa ; Xu, Rui Ming ; Krainer, Adrian R. / hnRNP A1 associates with telomere ends and stimulates telomerase activity. In: RNA. 2006 ; Vol. 12, No. 6. pp. 1116-1128.
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