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Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18488-18497. doi: 10.1073/pnas.1908275116. Epub 2019 Aug 26.

Single-cell imaging reveals unexpected heterogeneity of telomerase reverse transcriptase expression across human cancer cell lines.

Rowland TJ1,2,3, Dumbović G1,2, Hass EP1,2, Rinn JL1,2,3, Cech TR4,2,3.

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Department of Biochemistry, University of Colorado Boulder, Boulder, CO 80303.
BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80303.
Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, CO 80303.
Department of Biochemistry, University of Colorado Boulder, Boulder, CO 80303;


Telomerase is pathologically reactivated in most human cancers, where it maintains chromosomal telomeres and allows immortalization. Because telomerase reverse transcriptase (TERT) is usually the limiting component for telomerase activation, numerous studies have measured TERT mRNA levels in populations of cells or in tissues. In comparison, little is known about TERT expression at the single-cell and single-molecule level. To address this, we analyzed TERT expression across 10 human cancer lines using single-molecule RNA fluorescent in situ hybridization (FISH) and made several unexpected findings. First, there was substantial cell-to-cell variation in number of transcription sites and ratio of transcription sites to gene copies. Second, previous classification of lines as having monoallelic or biallelic TERT expression was found to be inadequate for capturing the TERT gene expression patterns. Finally, spliced TERT mRNA had primarily nuclear localization in cancer cells and induced pluripotent stem cells (iPSCs), in stark contrast to the expectation that spliced mRNA should be predominantly cytoplasmic. These data reveal unappreciated heterogeneity, complexity, and unconventionality in TERT expression across human cancer cells.


TERT; cancer; single-molecule imaging; telomerase; transcription

[Available on 2020-02-26]

Conflict of interest statement

Conflict of interest statement: T.R.C. is on the board of directors of Merck, Inc., and a consultant for Storm Therapeutics, neither of which provided funding for this study.

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