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Identification of an RNA aptamer binding hTERT-derived peptide and inhibiting telomerase activity in MCF7 cells

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Abstract

Human telomerase reverse transcriptase is an essential rate-limiting component of telomerase complex. hTERT protein in association with other proteins and the human telomerase RNA (hTR) shows telomerase activity, essential for maintaining genomic integrity in proliferating cells. hTERT binds hTR through a decapeptide located in the RID2 (RNA interactive domain 2) domain of N-terminal region. Since hTERT is essential for telomerase activity, inhibitors of hTERT are of great interest as potential anti-cancer agent. We have selected RNA aptamers against a synthetic peptide from the RID2 domain of hTERT by employing in vitro selection protocol (SELEX). The selected RNAs could bind the free peptide, as CD spectra suggested conformational change in aptamer upon RID2 binding. Extracts of cultured breast cancer cells (MCF7) expressing this aptamer showed lower telomerase activity as estimated by TRAP assay. hTERT-binding RNA aptamers hold promise as probable anti-cancer therapeutic agent.

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Abbreviations

hTR:

Human telomerase RNA component

hTERT:

Human telomerase reverse transcriptase

SELEX:

Systematic evolution of ligand by exponential enrichment

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Acknowledgements

The present study was supported by Project Grants from Department of Sciences and Technology and Grant received under UGC Resource Networking Centre, Government of India.

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Authors and Affiliations

  1. Applied Molecular Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India

    Akhil Varshney, Jyoti Bala, Baby Santosh, Ashima Bhaskar, Suresh Kumar & Pramod K. Yadava

  2. Molecular Genetics Laboratory, Institute of Cytogenetic and Preventive Oncology, Indian Council of Medical Research, Noida, Uttar Pradesh, 201301, India

    Suresh Kumar

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  1. Akhil Varshney
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Correspondence to Pramod K. Yadava.

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Varshney, A., Bala, J., Santosh, B. et al. Identification of an RNA aptamer binding hTERT-derived peptide and inhibiting telomerase activity in MCF7 cells. Mol Cell Biochem 427, 157–167 (2017). https://doi.org/10.1007/s11010-016-2907-7

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