کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5532198 1549659 2017 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research paperAlternative splicing of telomerase catalytic subunit hTERT generated by apoptotic endonuclease EndoG induces human CD4+ T cell death
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش گیاه شناسی
پیش نمایش صفحه اول مقاله
Research paperAlternative splicing of telomerase catalytic subunit hTERT generated by apoptotic endonuclease EndoG induces human CD4+ T cell death
چکیده انگلیسی


- Apoptotic endonuclease EndoG induces hTERT alternative splicing.
- EndoG expression correlates with the expression of hTERT splice variants.
- EndoG expression down-regulates telomerase activity in CD4+ T lymphocytes.
- Telomerase inhibition results in results in telomere loss.
- EndoG overexpression induces death of CD4+ T lymphocytes.

Telomerase activity is regulated by alternative splicing of its catalytic subunit human Telomerase Reverse Transcriptase (hTERT) mRNA. Induction of a non-active spliced hTERT leads to inhibition of telomerase activity. However, very little is known about the mechanism of hTERT mRNA alternative splicing. The aim of this study was to determine the role of the apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. A strong correlation was identified between EndoG expression levels and hTERT splice variants in human CD4+ and CD8+ T lymphocytes. Overexpression of EndoG in CD4+ T cells down-regulated the expression of the active full-length hTERT variant and up-regulated expression of the non-active spliced variant. A reduction in full-length hTERT transcripts down-regulated telomerase activity. Long-term in vitro cultivation of EndoG-overexpressing CD4+ T cells led to dramatically shortened telomeres, conversion of cells into a replicative senescence state, and activation of the BCL2/BAX-associated apoptotic pathway finally leading to cell death. These data indicated the participation of EndoG in alternative mRNA splicing of the telomerase catalytic subunit hTERT, regulation of telomerase activity and determination of cell fate.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Cell Biology - Volume 96, Issue 7, October 2017, Pages 653-664
نویسندگان
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