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, Benoît

doi:10.1038/575

Cited by 266 publications

(245 citation statements)

References 32 publications

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“…In a gel-shift assay using (TTAGGC) [2][3][4] telomeric repeats as probes, we found that 2.5 (TTAGGC) repeats was the minimum for HRP-1 binding. The affinity of HRP-1 binding was markedly higher when we used four (TTAGGC) repeats as a probe, consistent with previous reports that RNP A1 binding to telomeric DNA is length-dependent 9 (Fig. 1c).…”

supporting

confidence: 92%

“…Gel-shift assays were carried out using purified HRP-1 with the 32 P-end-labeled (TTAGGC) 4 probe in the presence of different amounts of unlabeled (TTAGGC) 4 (lanes 2-6) and nonspecific oligonucleotides (lanes [7][8][9][10][11]. The relative amounts of the competitors added are indicated.…”

mentioning

confidence: 99%

“…1a). These two proteins bind single-stranded telomeric DNA and are involved in telomere length regulation [8][9][10] . We confirmed that HRP-1 specifically bound to G-rich single-stranded telomeric DNA (Fig.…”

mentioning

confidence: 99%

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Long lifespan in worms with long telomeric DNA

et al. 2004

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Telomere length is a crucial factor in senescence 1-3 , but it has not been determined whether animals with long telomeres live longer than those with normal-length telomeres in the isogenic background of a given species. Here we show the effect of long telomeres on lifespan in the nematode Caenorhabditis elegans. We examined the effect of telomere length on lifespan by overexpressing HRP-1, a telomere-binding protein, which gradually increased telomere length in worms. Worms with longer telomeres lived longer. We confirmed that the extension of lifespan was due to the increased telomere length, and not to the overexpression of HRP-1 per se, by examining the lifespans of nontransgenic progeny of the transgenic worms, who retained the longer telomeres. The lifespan-extending effect of long telomeres was dependent on daf-16. The number of germ stem cells was not affected in worms with long telomeres, indicating that the telomere effect on lifespan is independent of germ stem cell cycling. Worms with long telomeres were more resistant to heat stress. Taken together, our results suggest that signaling may be initiated in postmitotic somatic cells by telomere length to regulate organismal lifespan.

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confidence: 92%

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confidence: 99%

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Long lifespan in worms with long telomeric DNA

et al. 2004

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“…Telomerase is composed of telomerase reverse transcriptase (hTERT) [27], telomerase-associated protein (TEP1) [9], and hnRNP A1 [21]. The de novo transcription of the hTERT gene is considered the dominant, rate-limiting step in telomerase activation whereas the expression of hTEP1 and hTR is constitutive [1,9].…”

Section: Introductionmentioning

confidence: 99%

Effects of histone deacetylase inhibitor FR901228 on the expression level of telomerase reverse transcriptase in oral cancer

Murakami

Asaumi

Kawai

et al. 2005

Cancer Chemother Pharmacol

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We speculated whether or not the expression level of telomerase reverse transcriptase (hTERT) would be modulated by agents targeting epigenetics in oral cancer cell lines. Although hTERT is known to be targeted by epigenetic changes, it remains unclear how chemoagents targeting epigenetics work on hTERT transcription. In the present study, the epigenetic effects of histone deacetylase (HDAC) inhibitor FR901228 on hTERT transcription were analysed by RT-PCR in oral cancer cell lines. The mRNA expression of hTERT was upregulated after exposure to FR901228 in hTERT-negative Hep2 cells, even in the hTERT highly expressed SAS and KB cells.Moreover, co-treatment of protein synthesis inhibitor cycloheximide (CHX) resulted in the induction of hTERT transcription by FR901228. This suggests that the induction of hTERT by FR901228 requires de novo protein synthesis to some extent and is more likely a direct than an indirect effect on epigenetic changes such as histone acetylation / deacetylation. We further examined the effect of FR901228 on c-myc protein, which is one of the main hTERT transcription activators. FR901228 repressed c-myc protein only in the absence of CHX, dependent of the enhancement of de novo protein synthesis. Our results indicate that c-myc protein is repressed indirectly by FR901228 but may not contribute FR901228-induced hTERT transcription. The present study showed that the HDAC inhibitor FR901228 induced the hTERT gene by a complex mechanism that involved other transcription factors except for c-myc, in addition to the inhibition of histone deacetylation.

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“…For example, hnRNP A1 was shown to bind single-stranded telomeric DNA and telomerase RNA [35]. Depletion of hnRNP A1 expression causes short telomeres and reduces telomerase activity [46,47]. It was postulated that binding of these hnRNPs to telomeres might help in recruiting telomerase to the telomeres.…”

Section: Discussionmentioning

confidence: 99%

The U3 small nucleolar ribonucleoprotein component Imp4p is a telomeric DNA-binding protein

Hsieh¹,

Tu²,

Lee³

et al. 2007

Biochemical Journal

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Imp4p is a component of U3 snoRNP (small nucleolar ribonucleoprotein) involved in the maturation of 18S rRNA. We have shown that Imp4p interacts with Cdc13p, a single-stranded telomere-binding protein involved in telomere maintenance. To understand the role of Imp4p in telomeres, we purified recombinant Imp4p protein and tested its binding activity towards telomeric DNA using electrophoretic mobility-shift assays. Our results showed that Imp4p bound specifically to single-stranded telomeric DNA in vitro. The interaction of Imp4p to telomeres in vivo was also demonstrated by chromatin immunoprecipitation experiments. Significantly, the binding of Imp4p to telomeres was not limited to yeast proteins, since the hImp4 (human Imp4) also bound to vertebrate single-stranded telomeric DNA. Thus we conclude that Imp4p is a novel telomeric DNA-binding protein that, in addition to its role in rRNA processing, might participate in telomere function.

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

Cited by 266 publications

References 32 publications

Long lifespan in worms with long telomeric DNA

Long lifespan in worms with long telomeric DNA

Effects of histone deacetylase inhibitor FR901228 on the expression level of telomerase reverse transcriptase in oral cancer

The U3 small nucleolar ribonucleoprotein component Imp4p is a telomeric DNA-binding protein

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