[Apoptotic endonuclease EndoG regulates alternative splicing of human telomerase catalytic subunit hTERT].

[Apoptotic endonuclease EndoG regulates alternative splicing of human telomerase catalytic subunit hTERT].
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[凋亡核酸内切酶EndoG调节人端粒酶催化亚基hTERT的选择性剪接]。

DOI:
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发表时间:
2017
期刊:
Biomeditsinskaia khimiia
影响因子:
--
通讯作者:
N. Sokolov
N. Sokolov
中科院分区:
--
文献类型:
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作者:
D. Zhdanov;D. A. Vasina;E. Orlova;V. Orlova;M. Pokrovskaya;S. Aleksandrova;N. Sokolov

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人端粒酶催化亚单位hTERT发生选择性剪接后,其功能丧失,导致端粒酶活性下降。然而,很少有人知道的hTERT前mRNA选择性剪接的机制。已知凋亡核酸内切酶EndoG参与该过程。本研究的目的是确定EndoG在调节hTERT选择性剪接中的作用。在CaCo-2细胞系中的EndoG过表达期间,在EndoG处理细胞质和细胞核之后,以及在细胞核与EndoG消化的细胞RNA孵育之后,确定b-缺失剪接变体的表达增加。在裸核和转染后的细胞中,47-mer RNA寡核苷酸诱导hTERT选择性剪接。鉴定了长的非编码RNA,即47-mer RNA寡核苷酸的前体。它的大小是1754个核苷酸。根据研究结果,提出了以下机制。hTERT前mRNA由编码DNA链转录,而长的非编码RNA由hTERT基因的模板链转录。EndoG酶解长的非编码RNA,产生与hTERT前mRNA外显子8和内含子8连接处互补的47-mer RNA寡核苷酸。47-mer RNA寡核苷酸与hTERT前体mRNA的相互作用引起选择性剪接。
Human telomerase catalytic subunit hTERT is subjected to alternative splicing results in loss of its function and leads to decrease of telomerase activity. However, very little is known about the mechanism of hTERT pre-mRNA alternative splicing. Apoptotic endonuclease EndoG is known to participate this process. The aim of this study was to determine the role of EndoG in regulation of hTERT alternative splicing. Increased expression of b-deletion splice variant was determined during EndoG over-expression in CaCo-2 cell line, after EndoG treatment of cell cytoplasm and nuclei and after nuclei incubation with EndoG digested cell RNA. hTERT alternative splicing was induced by 47-mer RNA oligonucleotide in naked nuclei and in cells after transfection. Identified long non-coding RNA, that is the precursor of 47-mer RNA oligonucleotide. Its size is 1754 nucleotides. Based on the results the following mechanism was proposed. hTERT pre-mRNA is transcribed from coding DNA strand while long non-coding RNA is transcribed from template strand of hTERT gene. EndoG digests long non-coding RNA and produces 47-mer RNA oligonucleotide complementary to hTERT pre-mRNA exon 8 and intron 8 junction place. Interaction of 47-mer RNA oligonucleotide and hTERT pre-mRNA causes alternative splicing.
DOI: 10.1038/sj.neo.7900113
发表时间: 2000-09-01
期刊: NEOPLASIA
影响因子: 4.8
作者:
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发表时间: 1994-12-23
期刊: SCIENCE
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