An RNA aptamer perturbs heat shock transcription factor activity in Drosophila melanogaster

Salamanca, H. Hans; Fuda, Nicholas J.; Shi, Hua; Lis, John T.

doi:10.1093/nar/gkr206

Cited by 18 publications

(26 citation statements)

References 52 publications

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“…In contrast, D01 RNA showed a typical binding curve with a dissociation constant ( K d ) of 273 (± 29) n m . This K d value is one‐two order higher than those of the previously reported RNA aptamers that inhibit intracellular DNA‐binding proteins (discussed below).…”

Section: Resultsmentioning

confidence: 65%

An inhibitory RNA aptamer against the lambda cI repressor shows transcriptional activator activity in vivo

Ohuchi

Suess

2017

FEBS Letters

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RNA aptamers are one of the promising components for constructing artificial genetic circuits. In this study, we developed a transcriptional activator based on an RNA aptamer against one of the most frequently applied repressor proteins, lambda phage cI. In vitro selection (Systematic Evolution of Ligands by EXponential enrichment) and following in vivo screening identified an RNA aptamer with the intended transcriptional activator activity from an RNA pool containing a 40-nucleotide long random region. Quantitative analysis showed a 35-fold elevation of reporter expression upon aptamer expression. These results suggest that the diversity of artificial transcriptional activators can be extended by employing RNA aptamers against repressor proteins to broaden the parts for constructing genetic circuits.

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Section: Resultsmentioning

confidence: 65%

An inhibitory RNA aptamer against the lambda cI repressor shows transcriptional activator activity in vivo

Ohuchi

Suess

2017

FEBS Letters

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“…This allows HSF1 to form trimers and translocate to the cell nucleus and activate transcription [7]. Its function is not only critical to overcome the proteotoxic effects of thermal stress, but also needed for proper animal development and the overall survival of cancer cells [100, 101]. It is worth mentioning that we have previously shown a synergistic effects of TSC1 as a neuroprotective agent.…”

mentioning

confidence: 99%

Proof-of Concept that an Acute Trophic Factors Intervention After Spinal Cord Injury Provides an Adequate Niche for Neuroprotection, Recruitment of Nestin-Expressing Progenitors and Regeneration

et al. 2016

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Trophic factor treatment has been shown to improve the recovery of brain and spinal cord injury (SCI). In this study, we examined the effects of TSC1 (a combination of insulin-like growth factor 1 and transferrin) 4 and 8 h after SCI at the thoracic segment level (T12) in nestin-GFP transgenic mice. TSC1 treatment for 4 and 8 h increased the number of nestin-expressing cells around the lesion site and prevented Wallerian degeneration. Treatment with TSC1 for 4 h significantly increased heat shock protein (HSP)-32 and HSP-70 expression 1 and 2 mm from lesion site (both, caudal and rostral). Conversely, the number of HSP-32 positive cells decreased after an 8-h TSC1 treatment, although it was still higher than in both, non-treated SCI and intact spinal cord animals. Furthermore, TSC1 increased NG2 expressing cell numbers and preserved most axons intact, facilitating remyelination and repair. These results support our hypothesis that TSC1 is an effective treatment for cell and tissue neuroprotection after SCI. An early intervention is crucial to prevent secondary damage of the injured SC and, in particular, to prevent Wallerian degeneration.

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“…The Drosophila MAPK pathway was previously reported by us to be affected by the HSF1 aptamer [14]. Likewise, the Lindquist and Gius Laboratories have demonstrated that HSF1 depletion also affect this pathway [22]–[23], [25].…”

Section: Resultsmentioning

confidence: 90%

Inhibiting Heat Shock Factor 1 in Human Cancer Cells with a Potent RNA Aptamer

et al. 2014

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Heat shock factor 1 (HSF1) is a master regulator that coordinates chaperone protein expression to enhance cellular survival in the face of heat stress. In cancer cells, HSF1 drives a transcriptional program distinct from heat shock to promote metastasis and cell survival. Its strong association with the malignant phenotype implies that HSF1 antagonists may have general and effective utilities in cancer therapy. For this purpose, we had identified an avid RNA aptamer for HSF1 that is portable among different model organisms. Extending our previous work in yeast and Drosophila, here we report the activity of this aptamer in human cancer cell lines. When delivered into cells using a synthetic gene and strong promoter, this aptamer was able to prevent HSF1 from binding to its DNA regulation elements. At the cellular level, expression of this aptamer induced apoptosis and abolished the colony-forming capability of cancer cells. At the molecular level, it reduced chaperones and attenuated the activation of the MAPK signaling pathway. Collectively, these data demonstrate the advantage of aptamers in drug target validation and support the hypothesis that HSF1 DNA binding activity is a potential target for controlling oncogenic transformation and neoplastic growth.

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An RNA aptamer perturbs heat shock transcription factor activity in Drosophila melanogaster

Cited by 18 publications

References 52 publications

An inhibitory RNA aptamer against the lambda cI repressor shows transcriptional activator activity in vivo

An inhibitory RNA aptamer against the lambda cI repressor shows transcriptional activator activity in vivo

Proof-of Concept that an Acute Trophic Factors Intervention After Spinal Cord Injury Provides an Adequate Niche for Neuroprotection, Recruitment of Nestin-Expressing Progenitors and Regeneration

Inhibiting Heat Shock Factor 1 in Human Cancer Cells with a Potent RNA Aptamer

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