A new component of telomerase assembly involved in the regulation of cellular senescence identified!

Telomerase defers the onset of telomere shortening and cellular senescence by adding telomeric repeat DNA to chromosome ends and its activation contributes to carcinogenesis. Telomerase minimally consists of the telomerase reverse transcriptase (TERT) and the telomerase RNA (TR). However, how telomerase is assembled is largely unknown.

To identify additional components of the human telomerase holoenzyme assembly, the scientists purified hTERT complexes from human cancer cells by co-immunoprecipitation (Co-IP) and examined hTERT-interacting partners with mass spectrometry.

They identified PES1 (also known as Pescadillo), which as a component of active telomerase complex, has been shown to be upregulated in many cancers and can regulate cell cycle progression as well as the synthesis and maturation of ribosome.

They found that PES1 increased telomerase activity without affecting the expression of hTERT or hTR. Moreover, PES1 regulates telomere length and cellular senescence. Mechanistically, PES1 facilitates telomerase assembly by promotion of direct interaction between hTERT and hTR.

High PES1 expression in cancer patients is associated with worse overall and relapse-free survival. Cancer cell growth is inhibited by knocking down PES1 in vitro and in nude mice. Thus, targeting PES1 may open a new avenue for cancer treatment.

http://english.cas.cn/newsroom/research_news/201907/t20190703_212597.shtml

https://advances.sciencemag.org/content/5/5/eaav1090