title: Human cells lacking coilin and Cajal bodies are proficient in telomerase assembly, trafficking and telomere maintenance.
abstract: The RNA component of human telomerase (hTR) localizes to Cajal bodies, and it has been proposed that Cajal bodies play a role in the assembly of telomerase holoenzyme and telomerase trafficking. Here, the role of Cajal bodies was examined in Human cells deficient of coilin (i.e. coilin-knockout (KO) cells), in which no Cajal bodies are detected. In coilin-KO cells, a normal level of telomerase activity is detected and interactions between core factors of holoenzyme are preserved, indicating that telomerase assembly occurs in the absence of Cajal bodies. Moreover, dispersed hTR aggregates and forms foci specifically during S and G2 phase in coilin-KO cells. Colocalization of these hTR foci with telomeres implies proper telomerase trafficking, independent of Cajal bodies. Therefore, telomerase adds similar numbers of TTAGGG repeats to telomeres in coilin-KO and controls cells. Overexpression of TPP1-OB-fold blocks cell cycle-dependent formation of hTR foci and inhibits telomere extension. These findings suggest that telomerase assembly, trafficking and extension occur with normal efficiency in Cajal bodies deficient human cells. Thus, Cajal bodies, as such, are not essential in these processes, although it remains possible that non-coilin components of Cajal bodies and/or telomere binding proteins (e.g. TPP1) do play roles in telomerase biogenesis and telomere homeostasis.
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, Cooperative Innovation Center for High Performance Computing, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
authors.forename: Yanlian
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, P.R. China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, Cooperative Innovation Center for High Performance Computing, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, Cooperative Innovation Center for High Performance Computing, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, Cooperative Innovation Center for High Performance Computing, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, Cooperative Innovation Center for High Performance Computing, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Songyang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, Cooperative Innovation Center for High Performance Computing, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ma
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, P.R. China.
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, Cooperative Innovation Center for High Performance Computing, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China zhaoy82@mail.sysu.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D020541:Coiled Bodies / Q000502:physiology*; D006801:Humans; D018832:Molecular Chaperones; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D016196:S Phase / Q000235:genetics; D000089804:Shelterin Complex; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000201:enzymology; D059505:Telomere Homeostasis; D034501:Telomere-Binding Proteins / Q000378:metabolism
chemical_list: C495876:ACD protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; C068921:p80-coilin; D019098:Telomerase; C535133:WRAP53 protein, human