Brief Background
Discovered by Carol Greider and Liz Blackburn in 1985, telomerase is a unique ribonucleoprotein (RNP) enzyme that adds telomeric repeats to the 3' end of chromosomes to counteract the DNA degradation that occurs due to the end replication problem. The Telomerase RNP contains two essential core components, the telomerase reverse transcriptase (TERT) and the telomerase RNA (TR), along with other species-specific telomerase associated proteins. The TR component contains a template region that is complementary to the telomeric DNA sequence, while TERT contains the catalytic reverse transcriptase domain responsible for nucleotide addition. The TERT and TR components are sufficient to reconstitute activity in vitro, however a variety of species-specific proteins are necessary for telomerase function in vivo and are thus thought to be involved in the regulation and biogenesis of telomerase. Telomerase is active in immortal cells such as germline and stem cells. Telomerase activity is also found in more than 85% of tumors making it a potential drug target for cancer therapy. Moreover, mutations in telomerase genes have been associated with a multitude of diseases including aplastic anaemia, dyskeratosis congenita, and idiopathic pulmonary fibrosis.
Animation
The telomerase reaction within vertebrates and ciliates is processive, iteratively adding hundreds of telomeric repeats onto the DNA strand. During a processive reaction, the DNA strand (blue) anneals to the alignment region in the TR (pink), the catalytic TERT protein (grey) reverse transcribes the RNA template (red), adding 6 deoxyribonucleotides (blue) to the DNA strand. After extension, the DNA dissociates from the RNA and the newly synthesized DNA (blue) anneals to alignment region in the TR (pink), ready for reverse transcription to occur.
Research milestones
Database content
The site is divided into 5 major pages: sequences, alignments, structures, diseases, and researchers. The sequences page is further broken down into separate pages for each of the components of telomerase. Each of these pages lists information related to the component, the RNA or amino acid sequence, the genbank accession number, and a link to the record at the National Center for Biotechnology Information (NCBI). The alignments page contains multiple RNA and amino acid sequence alignments based on both sequence and structural similarities. The structures page is separated into secondary and tertiary structures with a listing of files in .pdf, .jpg, and .pdb format. The diseases page is divided into the telomerase components and contains a listing of mutations and their associated clinical phenotype seen in patients. The researchers page is a listing of telomerase researchers and their affiliation.
The sequences presented within the database were used for the construction of the alignments. These alignments were then used to construct the phylogenetic trees and the secondary structures. All referenced materials used are cited and linked to the primary papers. The database is an ongoing project and will be updated continuously. The date of the last update to the site is located in the top right corner of the screen.
Publication rate
PubMed search term: telomere[Title/Abstract]
PubMed search term: telomerase[Title/Abstract]
Nomenclature
A standard nomenclature is used throughout the online database for consistency and clarity. Homologous proteins are given a single name for simplicity. The abbreviations of TR and TERT, for the telomerase RNA and reverse transcriptase, are used for brevity.
| TR | TERC | TER | TER1 | TLC1 | |||
|---|---|---|---|---|---|---|---|
| TERT | TRT | Est2 | p123 | TP2 | TCS1 | ||
| Gar1 | Nola1 | ||||||
| NHP2 | Nola2 | L7Ae | |||||
| Nop10 | Nola3 | ||||||
| dyskerin | Nola4 | Cbf5 | DKC1 | NAP57 | |||
| DnaK | hsp70 | ||||||
| Est1A | Smg6 | ||||||
| Est1B | Smg5 | ||||||
| TRF1 | TERF1 | TRBF1 | TRF | PIN2 | FLJ41416 | ||
| TRF2 | TERF2 | TRBF2 | |||||
| Pot1 | TEBPα | ||||||
| TINF2 | TIN2 | ||||||
| Rap1 | TERF2IP | DRIP5 | |||||
| TPP1 | TEBPβ | CLN2 | GIG1 | LPIC | |||
| MDV | GaHV (Gallid herpesvirus) | ||||||
Listed in gold is the nomenclature in use within the database with other common names and homologs to the right.
Acknowledgements
We acknowledge support provided by National Science Foundation (NSF) from 2007 to 2013, 2016 to 2019 and 2021 to present.