Expression of mouse telomerase reverse transcriptase during development, differentiation and proliferation.
We have identified the mouse telomerase reverse transcriptase component (mTERT) and demonstrate both substantial sequence homology to the human ortholog (hTERT), and the presence of reverse transcriptase and telomerase specific motifs. Furthermore, we show functional interchangeability with hTERT in in vitro telomerase reconstitution experiments, as mTERT produces strong telomerase activity in combination with the human telomerase RNA component hTR. The mouse TERT is widely expressed at low levels in adult tissues, with greatest abundance during embryogenesis and in adult thymus and intestine. The mTERT component mRNA levels were regulated during both differentiation and proliferation, while mTR levels remained constant throughout both processes. Comparison of mTERT and mTR levels to telomerase activity indicates that mTERT expression is more tightly linked to the regulation of telomerase activity during these processes than is mTR. In contrast to the situation in human cell cultures, mTERT transcript levels are present at readily detectable levels in primary cultured cells and are not upregulated following crisis. The widespread expression of mTERT in primary cells and mouse tissues could explain the increased frequency of spontaneous immortalization of mouse cells in culture and tumorigenesis in vivo.
Greenberg
R A
RA
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Allsopp
R C
RC
Chin
L
L
Morin
G B
GB
DePinho
R A
RA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D016922:Cellular Senescence; D002874:Chromosome Mapping; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D017386:Sequence Homology, Amino Acid; D013154:Spleen; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D008934:Mitogens; D009698:Nucleoproteins; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse; D013755:Tetradecanoylphorbol Acetate