Inhibition of telomerase activity by splice-switching oligonucleotides targeting the mRNA of the telomerase catalytic subunit affects proliferation of human CD4+ T lymphocytes

Telomerase activity is regulated at the mRNA level by alternative splicing (AS) of its catalytic subunit hTERT. The aim of this study was to define the ability of splice-switching oligonucleotides (SSOs) that pair with hTERT pre-mRNA to induce AS and inhibit telomerase activity in human CD4+ T lymphocytes. SSOs that blocked the binding of a single splicing regulatory protein, SRp20 or SRp40, to its site within intron 8 of hTERT pre-mRNA demonstrated rather moderate capacities to induce AS and inhibit telomerase. However, a SSO that blocked the interaction of both SRp20 and SRp40 proteins with pre-mRNA was the most active. Cultivation of lymphocytes with spliced hTERT and inhibited telomerase resulted in the reduction of proliferative activity without significant induction of cell death. These results should facilitate further investigation of telomerase activity regulation, and antitelomerase SSOs could become promising agents for antiproliferative cell therapy. © 2019 Elsevier Inc.

Авторы
Редакторы
-
Издательство
-
Номер выпуска
3
Язык
Английский
Страницы
790-796
Статус
Опубликовано
Подразделение
-
Номер
-
Том
509
Год
2019
Организации
  • 1 Institute of Biomedical Chemistry, 10/8 Pogodinskaya st, Moscow, 119121, Russian Federation
  • 2 Рeoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, Moscow, 117198, Russian Federation
  • 3 N.N. Blokhin Cancer Research Center, 24 Kashirskoe Shosse, Moscow, 115478, Russian Federation
Ключевые слова
Alternative splicing; Lymphocytes; Proliferation; Splice-switching oligonucleotides; Telomerase
Дата создания
04.02.2019
Дата изменения
04.02.2019
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/36066/