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TERRA mimicking ssRNAs prevail over the DNA substrate for telomerase in vitro due to interactions with the alternative binding siteстатья
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 6 мая 2016 г.
- Авторы: Azhibek Dulat, Skvortsov Dmitry, Andreeva Anna, Zatsepin Timofei, Arutyunyan Alexandr, Zvereva Maria, Dontsova Olga
- Журнал: Journal of Molecular Recognition
- Том: 29
- Номер: 6
- Год издания: 2016
- Издательство: John Wiley & Sons Inc.
- Местоположение издательства: United States
- Первая страница: 242
- Последняя страница: 247
- DOI: 10.1002/jmr.2521
- Аннотация: Telomerase is a key component of the telomere length maintenance system in the majority of eukaryotes. Telomerase displays maximal activity in stem and cancer cells with high proliferative potential. In humans, telomerase activity is regulated by various mechanisms, including the interaction with telomere ssDNA overhangs that contain a repetitive G-rich sequence, and with noncoding RNA, Telomeric repeat-containing RNA (TERRA), that contains the same sequence. So these nucleic acids can compete for telomerase RNA templates in the cell. In this study, we have investigated the ability of different model substrates mimicking telomere DNA overhangs and TERRA RNA to compete for telomerase in vitro through a previously developed telomerase inhibitor assay. We have shown in this study that RNA oligonucleotides are better competitors for telomerase that DNA ones as RNA also use an alternative binding site on telomerase, and the presence of 2′-OH groups is significant in these interactions. In contrast to DNA, the possibility of forming intramolecular G-quadruplex structures has a minor effect for RNA binding to telomerase. Taking together our data, we propose that TERRA RNA binds better to telomerase compared with its native substrate – the 3′-end of telomere DNA overhang. As a result, some specific factor may exist that participates in switching telomerase from TERRA to the 3′-end of DNA for telomere elongation at the distinct period of a cell cycle in vivo.
- Добавил в систему: Зацепин Тимофей Сергеевич