Alternatively spliced telomerase reverse transcriptase variants lacking telomerase activity stimulate cell proliferation.
Eight human and six chicken novel alternatively spliced (AS) variants of telomerase reverse transcriptase (TERT) were identified, including a human variant (Δ4-13) containing an in-frame deletion which removed exons 4 through 13, encoding the catalytic domain of telomerase. This variant was expressed in telomerase-negative normal cells and tissues as well as in transformed telomerase-positive cell lines and cells which employ an alternative method to maintain telomere length. The overexpression of the Δ4-13 variant significantly elevated the proliferation rates of several cell types without enhancing telomerase activity, while decreasing the endogenous expression of this variant by use of small interfering RNA (siRNA) technology reduced cell proliferation. The expression of the Δ4-13 variant stimulated Wnt signaling. In chicken cells, AS TERT variants containing internal deletions or insertions that eliminated or reduced telomerase activity also enhanced cell proliferation. This is the first report that naturally occurring AS TERT variants which lack telomerase activity stimulate cell proliferation.
Section of Molecular Genetics and Microbiology, School of Biological Science, and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, USA.
Radmila
R
Hrdlicková
Jirí
J
Nehyba
Henry R
HR
Bose
D017398:Alternative Splicing; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014644:Genetic Variation; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D060449:Wnt Signaling Pathway
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C509186:TERT protein, human; D019098:Telomerase