hnRNP A2, a potential ssDNA/RNA molecular adapter at the telomere

Moran-Jones, Kim

doi:10.1093/nar/gki203

Cited by 78 publications

(91 citation statements)

References 62 publications

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“…In our hands, both RRM1 and RRM2 of UP1 are required for binding to TR2 by EMSA (Fig. 2), as was shown also for the RRMs of hnRNP A2 (Moran-Jones et al 2005). We also found in the depletion experiment that hnRNP A1 can be separated completely from hTR, suggesting that they do not stably interact.…”

Section: How Does Hnrnp A1 Stimulate the Telomerase Reaction?supporting

confidence: 81%

hnRNP A1 associates with telomere ends and stimulates telomerase activity

Zhang

Manche

et al. 2006

RNA

154

144

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Telomerase is a ribonucleoprotein enzyme complex that reverse-transcribes an integral RNA template to add short DNA repeats to the 39-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.

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Section: How Does Hnrnp A1 Stimulate the Telomerase Reaction?supporting

confidence: 81%

hnRNP A1 associates with telomere ends and stimulates telomerase activity

Zhang

Manche

et al. 2006

RNA

154

144

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“…4 ). As both hnRNP M and D / AUF1 have been previously shown to bind to single-stranded DNA 11,20,30 , absence of these two hnRNPs from telomeres may activate a mechanism that recruits TERRA to telomeres, possibly to increase telomere protection (see Fig. 5 for decreased telomere damage foci in hnRNP M and D / AUF knockdowns).…”

Section: Resultsmentioning

confidence: 99%

TERRA transcripts are bound by a complex array of RNA-binding proteins

2010

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Telomeres are transcribed from the telomeric C-rich strand, giving rise to UUAGGG repeatcontaining telomeric transcripts or TERRA, which are novel structural components of telomeres. TERRA abundance is highly dependent on developmental status (including nuclear reprogramming), telomere length, cellular stresses, tumour stage and chromatin structure. However, the molecular mechanisms and factors controlling TERRA levels are still largely unknown. In this study, we identify a set of RNA-binding proteins, which endogenously bind and regulate TERRA in the context of primary mouse embryonic fi broblasts. The identifi cation was carried out by biotin pull-down assays followed by LC-MALDI TOF / TOF mass spectrometry. Different members of the heterogeneous nuclear ribonucleoprotein family are among the ribonucleoprotein family that bind more abundantly to TERRA. Downregulation of TERRA-bound RBPs by small interfering RNA further shows that they can impact on TERRA abundance, their location and telomere lengthening. These fi ndings anticipate an impact of TERRA-associated RBPs on telomere biology and telomeres diseases, such as cancer and aging.

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“…HnRNPA2 associated with single-stranded DNA (ssDNA) does not bind to SET HnRNPA2 is an RNA-and an ssDNA-binding protein (Moran-Jones et al, 2005). Thus, we aimed to analyse whether SET could affect the association between hnRNPA2 and ssDNA.…”

Section: Identification Of Hnrnpa2 As a Set-binding Proteinmentioning

confidence: 99%

Heterogeneous nuclear ribonucleoprotein A2 is a SET-binding protein and a PP2A inhibitor

et al. 2005

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The oncoprotein SET participates in a diversity of cellular functions including cell proliferation. Its role on cell cycle progression is likely mediated by inhibiting cyclin B-cdk1 and the protein phosphatase 2A (PP2A). On identifying new SET cellular partners, we found that SET interacts in vitro and in vivo with the heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2); a protein involved in various aspects of mRNA biogenesis. The SET-binding region of hnRNPA2 is the RNP1 sequence that belongs to the RNA-binding domain (RBD) of this protein. We also found that hnRNPA2 has much higher affinity for singlestanded DNA than for SET. On analysing the effect of hnRNPA2 on PP2A inhibition by SET, we observed that hnRNPA2 cooperates with SET on PP2A inhibition. This is because we found that hnRNPA2 is also a PP2A inhibitor. HnRNPA2 interacts with PP2A by the RNP1 sequence; however, to inhibit PP2A activity, the complete RBD is needed. We also observed that overexpression of hnRNPA2 inhibits PP2A activity and stimulates cell proliferation. Interestingly, the overexpression of the complete RBD is sufficient to stimulate proliferation. As hnRNPA2 is overexpressed in a variety of human tumors, our results suggest that hnRNPA2 might participate in oncogenesis by stimulating cell proliferation.

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hnRNP A2, a potential ssDNA/RNA molecular adapter at the telomere

Cited by 78 publications

References 62 publications

hnRNP A1 associates with telomere ends and stimulates telomerase activity

hnRNP A1 associates with telomere ends and stimulates telomerase activity

TERRA transcripts are bound by a complex array of RNA-binding proteins

Heterogeneous nuclear ribonucleoprotein A2 is a SET-binding protein and a PP2A inhibitor

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