Jalink Marit, Ge Zheng, Liu Cheng, Björkholm Magnus, Gruber Astrid, Xu Dawei
Department of Medicine, Division of Haematology, Karolinska University Hospital Solna and Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Biochem Biophys Res Commun. 2007 Feb 23;353(4):999-1003. doi: 10.1016/j.bbrc.2006.12.149. Epub 2006 Dec 27.
Alternative splicing of telomerase reverse transcriptase (hTERT) mRNA is known to contribute to regulation of telomerase activity in normal and cancerous cells, however, previous studies indicated that normal human T and B cells exhibited constitutive expression of full-length hTERT mRNA without splicing variants and that activation of telomerase upon stimulation of the cells was due to the shuttling of hTERT protein from cytoplasm to nucleus [Proc. Natl. Acad. Sci. USA 96 (1999) 5147; J. Immunol. 166 (2001) 4826]. We found that typical variants of hTERT mRNA were widespread in human lymphocyte-derived cell lines and normal stimulated T cells. In activated T cells, induction of the full-length hTERT mRNA was coupled with increased hTERT protein expression and telomerase activity. Collectively, human normal and malignant lymphocytes, like other human cells, express splicing variants of hTERT mRNA and require transcriptional activation of the hTERT gene to acquire telomerase activity.
已知端粒酶逆转录酶(hTERT)mRNA的可变剪接有助于调节正常细胞和癌细胞中的端粒酶活性,然而,先前的研究表明,正常人T细胞和B细胞表现出全长hTERT mRNA的组成型表达,没有剪接变体,并且细胞刺激后端粒酶的激活是由于hTERT蛋白从细胞质穿梭到细胞核[美国国家科学院院刊96(1999)5147;免疫学杂志166(2001)4826]。我们发现hTERT mRNA的典型变体在人淋巴细胞衍生的细胞系和正常刺激的T细胞中广泛存在。在活化的T细胞中,全长hTERT mRNA的诱导与hTERT蛋白表达增加和端粒酶活性增加相关。总体而言,人类正常和恶性淋巴细胞与其他人类细胞一样,表达hTERT mRNA的剪接变体,并且需要hTERT基因的转录激活来获得端粒酶活性。