Abstract
Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6–19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw.
Highlights
IntroductionTelomerase is a ribonucleoprotein comprised of the TERT (telomerase reverse transcriptase) protein and a TR (telomerase RNA) subunit
Telomerase is a ribonucleoprotein comprised of the TERT protein and a TR subunit
We demonstrate that telomerase activity (TA) and hTR both decrease during fetal brain development, while WT hTERT and α-spliced TERT seemed to co-exist in adult human brain
Summary
Telomerase is a ribonucleoprotein comprised of the TERT (telomerase reverse transcriptase) protein and a TR (telomerase RNA) subunit. Its main and best understood function is telomere maintenance. Telomerase activity is high during early fetal development but down regulated soon afterwards in most somatic cell types. Telomerase is still active in some adult tissues such as many immune cells, endothelium and inducible in adult stem cells. It is known that the TERT protein has various telomere-independent functions (for review see [1]). One of them seems to be a protective function of TERT protein in the brain, which could have implications for brain ageing and neurodegenerative diseases [2,3]
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