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Tissue‐specific alternate splicing of human telomerase reverse transcriptase (hTERT) influences telomere lengths during human development
Author(s) -
Ulaner Gary A.,
Hu JiFan,
Vu Thanh H.,
Giudice Linda C.,
Hoffman Andrew R.
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1103>3.0.co;2-v
Subject(s) - telomere , telomerase reverse transcriptase , telomerase , reverse transcriptase , biology , rna splicing , genetics , rna , dna , gene
Direct genetic manipulations have shown that telomerase‐mediated telomere elongation plays a key role in determining cellular replicative capacity and senescence. The mechanisms regulating the production of an active telomerase enzyme are still predominantly unknown, although roles for transcriptional control of hTERT, alternative‐splicing of hTERT transcripts, and post‐translational phosphorylation of hTERT protein have been advocated. Here we show that hTERT is alternatively spliced in specific patterns by different tissue types during human development. Alternative splicing often prohibits the expression of hTERT protein containing functional reverse transcriptase domains. In these instances, telomerase activity is absent, leading to shortening of telomeres. The specific pattern of hTERT mRNA variants in human development provides evidence that alternative splicing is non‐random and participates in the regulation of telomerase activity. © 2001 Wiley‐Liss, Inc.