Telomerase activity in human development is regulated by human telomerase reverse transcriptase (hTERT) transcription and by alternate splicing of hTERT transcripts. 1998

G A Ulaner, and J F Hu, and T H Vu, and L C Giudice, and A R Hoffman
Veterans Affairs Palo Alto Health Care System, and Department of Medicine, Stanford University, California 94304, USA.

The correlation between telomerase activity, telomere lengths, and cellular replicative capacity has led to the theory that maintenance of telomere lengths by telomerase acts as a molecular clock to control replicative capacity and senescence. Regulation of this molecular clock may have applications in the treatment of cell aging and tumorigenesis, although little is presently known about the regulation of telomerase activity. To investigate possible mechanisms of regulation, we examined telomerase activity and the expression of the human telomerase RNA subunit and the human telomerase reverse transcriptase protein (hTERT) during human fetal heart, liver, and kidney development. The human telomerase RNA subunit is expressed in all three tissues at all gestational ages examined. hTERT expression correlates with telomerase activity in the liver, where both are expressed at all ages surveyed, and in the heart, where both are present until the 11th gestational week but not thereafter. However, although telomerase activity in the kidney is suppressed after the 15th gestational week, the hTERT transcript can be detected until at least the 21st week. Reverse transcription-PCR using primers within the reverse transcriptase domain of hTERT show the presence of multiple alternately spliced transcripts in these tissues, corresponding to full-length message as well as spliced messages with critical reverse transcriptase motifs deleted. Of note, telomerase activity in the kidney is only present at those gestational ages when full-length hTERT message is expressed (until approximately week 15), with spliced transcripts continuing to be expressed at later stages of development. The tissue-specific and gestational-age dependent expression of hTERT mRNA seen in human development suggests the presence of at least two regulatory mechanisms controlling the activity of telomerase: transcriptional control of the hTERT gene and alternate splicing of hTERT transcripts.

UI MeSH Term Description Entries
D009928 Organ Specificity Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen. Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D005333 Fetus The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN. Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal
D005865 Gestational Age The age of the conceptus, beginning from the time of FERTILIZATION. In clinical obstetrics, the gestational age is often estimated from the onset of the last MENSTRUATION which is about 2 weeks before OVULATION and fertilization. It is also estimated to begin from fertilization, estrus, coitus, or artificial insemination. Embryologic Age,Fetal Maturity, Chronologic,Chronologic Fetal Maturity,Fetal Age,Maturity, Chronologic Fetal,Age, Embryologic,Age, Fetal,Age, Gestational,Ages, Embryologic,Ages, Fetal,Ages, Gestational,Embryologic Ages,Fetal Ages,Gestational Ages
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012313 RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) RNA, Non-Polyadenylated,Ribonucleic Acid,Gene Products, RNA,Non-Polyadenylated RNA,Acid, Ribonucleic,Non Polyadenylated RNA,RNA Gene Products,RNA, Non Polyadenylated
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D017398 Alternative Splicing A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different. RNA Splicing, Alternative,Splicing, Alternative,Alternate Splicing,Nested Transcripts,Alternate Splicings,Alternative RNA Splicing,Alternative RNA Splicings,Alternative Splicings,Nested Transcript,RNA Splicings, Alternative,Splicing, Alternate,Splicing, Alternative RNA,Splicings, Alternate,Splicings, Alternative,Splicings, Alternative RNA,Transcript, Nested,Transcripts, Nested

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