Yusheng Zhu ¹, Rebecca L. Tomlinson ¹, Andrew A. Lukowiak ¹, Rebecca M. Terns ¹, and Michael P. Terns ^1,*

¹ Departments of Biochemistry and Molecular Biology, and Genetics, University of Georgia, Athens, GA 30602, USA

* Corresponding author. E-mail address:     mterns@bmb.uga.edu

Telomerase synthesizes telomeric DNA repeats at the ends of eukaryotic chromosomes. The RNA component of the enzyme (hTR) provides the template for telomere synthesis, which is catalyzed by telomerase reverse
transcriptase (hTERT). Little is known regarding the subcellular localization of hTR and hTERT, and the pathway by which telomerase is assembled. Here we report the first glimpse of the detailed subcellular localization of endogenous hTR in human cells, which we obtained by fluorescence in situ hybridization (FISH). Our studies have revealed a distinctive hTR localization pattern in cancer cells. We have found that hTR accumulates within intranuclear foci called Cajal bodies in all typical tumor-derived cell lines examined (in which telomerase is active), but not in primary or ALT cells (where little or no hTERT is present). Accumulation of hTR in the Cajal bodies of primary cells is induced when hTERT is ectopically expressed. Moreover, we report that hTERT is also found in Cajal bodies. Our data suggests that Cajal bodies are involved in the assembly and/or function of human telomerase.

Additional References:

1. Shippen-Lentz D, and Blackburn EH, "Functional Evidence for an RNA Template in Telomerase".

2. Lue NF, "Sequence-Specific and Conformation-Dependent Binding of Yeast Telomerase RNA to Single-Stranded Telomeric DNA".

3. Mitchell JR, and Collins K, "Human Telomerase Activation Requires Two Independent Interactions between Telomerase RNA and Telomerase Reverse Transcriptase".

4. Oh H, Taffet GE, Youker KA, Entman ML, Overbeek PA, Michael LH, and Schneider MD, "Telomerase Reverse Transcriptase Promotes Cardiac Muscle Cell Proliferation, Hypertrophy, and Survival".

5. Lanz RB, Razani B, Goldberg AD, and O'Malley BW, "Distinct RNA Motifs are Important for Coactivation of Steroid Hormone Receptors by Steroid Receptor RNA Activator (SRA)".

6. Hovsepian JA, and Frenster JH, "RNA-Induced Melting of DNA during Selective Gene Transcription".

7. Saha S, Ansari AZ, Jarell KA, and Ptashne M, "RNA Sequences that Work as Transcriptional Activating Regions".

8. Gottesfeld JM, and Barbas CF III, "RNA as a Transcriptional Activator".

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euchromatin: "the most active portion of the genome within the cell nucleus".