Coding non-coding human telomerase RNAтезисы доклада Тезисы

Работа с тезисами доклада


[1] Coding non-coding human telomerase rna / N. Yulia, R. Maria, V. Daria et al. // 42nd FEBS Congress From molecules to cells and back, Иерусалим, Израиль, 10-14 сентября 2017. — 2017. — P. 13–13. Telomeres are shortened after each round of cell division, and once telomeres reach a critically short length, the cell either dies by apoptosis or stops dividing and senesces. Telomeres are maintained in most eukaryotes by a specific enzyme called telomerase. The telomerase holoenzyme is a ribonucleoprotein complex (RNP) that possesses a reverse transcriptase activity and carries its own RNA template (TR, TER, TERC) for telomere repeat addition. Telomerase is repressed in most normal cells, but upregulated in many tumor progenitor cells, which enables the continued and uncontrolled proliferation of the malignant cells that provide tumor growth and progression. We have found that the human telomerase RNA (hTR), also known as noncoding RNA, contains open reading frame. The length of ORF in hTR is 366 nucleotides. This protein was named hTERP (human TElomerase RNA Protein). The molecular weight of hTERP is 13 kDa. We demonstrated the existence of hTERP in eukaryotic cells by different molecular biology techniques. Francesca S. Gazzaniga and Elizabeth H. Blackburn have previously shown that hTR plays an antiapoptotic role in CD4 T-cells independently from telomerase catalytic activity. Our data allow to propose that the hTERP may be a player in regulation of cell survival during apoptosis-autophagy crosstalk. Exogenous expression of wild type telomerase RNA protects cells from drug-induced apoptosis, but the expression of telomerase RNA mutated at start codon does not. In addition, we analyzed the biological role of endogenous protein encoded by human telomerase RNA using CRISPR/Cas system and investigated the potential interaction partners. Our preliminary data indicates that hTERP can influence an autophagosome formation. In conclusions, our results show that the human telomerase RNA translation product may be a player in the regulations of cell survival, which is crucial in cancer and aging treatment.

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