Most cited article - PubMed ID 29948659
An armadillo-domain protein participates in a telomerase interaction network
Telomerase, an essential enzyme that maintains chromosome ends, is important for genome integrity and organism development. Various hypotheses have been proposed in human, ciliate and yeast systems to explain the coordination of telomerase holoenzyme assembly and the timing of telomerase performance at telomeres during DNA replication or repair. However, a general model is still unclear, especially pathways connecting telomerase with proposed non-telomeric functions. To strengthen our understanding of telomerase function during its intracellular life, we report on interactions of several groups of proteins with the Arabidopsis telomerase protein subunit (AtTERT) and/or a component of telomerase holoenzyme, POT1a protein. Among these are the nucleosome assembly proteins (NAP) and the minichromosome maintenance (MCM) system, which reveal new insights into the telomerase interaction network with links to telomere chromatin assembly and replication. A targeted investigation of 176 candidate proteins demonstrated numerous interactions with nucleolar, transport and ribosomal proteins, as well as molecular chaperones, shedding light on interactions during telomerase biogenesis. We further identified protein domains responsible for binding and analyzed the subcellular localization of these interactions. Moreover, additional interaction networks of NAP proteins and the DOMINO1 protein were identified. Our data support an image of functional telomerase contacts with multiprotein complexes including chromatin remodeling and cell differentiation pathways.
- Keywords
- Arabidopsis, chromatin, folding, mitochondria, protein–protein interaction, replication, telomerase, transport,
- MeSH
- Arabidopsis metabolism MeSH
- Transcription, Genetic MeSH
- Golgi Apparatus metabolism MeSH
- Telomere Homeostasis MeSH
- Protein Interaction Maps MeSH
- Mitochondria metabolism MeSH
- Multiprotein Complexes metabolism MeSH
- Nucleosomes metabolism MeSH
- Peptides metabolism MeSH
- RNA Processing, Post-Transcriptional genetics MeSH
- Arabidopsis Proteins chemistry metabolism MeSH
- Telomere-Binding Proteins metabolism MeSH
- Gene Expression Regulation, Plant MeSH
- DNA Replication MeSH
- Chromatin Assembly and Disassembly MeSH
- Ribosomes metabolism MeSH
- Telomerase metabolism MeSH
- Protein Binding MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Multiprotein Complexes MeSH
- Nucleosomes MeSH
- Peptides MeSH
- Arabidopsis Proteins MeSH
- Telomere-Binding Proteins MeSH
- Telomerase MeSH
The canonical DNA polymerases involved in the replication of the genome are unable to fully replicate the physical ends of linear chromosomes, called telomeres. Chromosomal termini thus become shortened in each cell cycle. The maintenance of telomeres requires telomerase-a specific RNA-dependent DNA polymerase enzyme complex that carries its own RNA template and adds telomeric repeats to the ends of chromosomes using a reverse transcription mechanism. Both core subunits of telomerase-its catalytic telomerase reverse transcriptase (TERT) subunit and telomerase RNA (TR) component-were identified in quick succession in Tetrahymena more than 30 years ago. Since then, both telomerase subunits have been described in various organisms including yeasts, mammals, birds, reptiles and fish. Despite the fact that telomerase activity in plants was described 25 years ago and the TERT subunit four years later, a genuine plant TR has only recently been identified by our group. In this review, we focus on the structure, composition and function of telomerases. In addition, we discuss the origin and phylogenetic divergence of this unique RNA-dependent DNA polymerase as a witness of early eukaryotic evolution. Specifically, we discuss the latest information regarding the recently discovered TR component in plants, its conservation and its structural features.
- Keywords
- evolution, plant TERT, plant TR., telomerase, telomerase RNA (TR), telomerase reverse transcriptase (TERT),
- MeSH
- Biological Evolution * MeSH
- History, 20th Century MeSH
- History, 21st Century MeSH
- Eukaryota classification genetics metabolism MeSH
- Phylogeny MeSH
- Humans MeSH
- RNA physiology MeSH
- Telomerase chemistry physiology MeSH
- Telomere metabolism MeSH
- Animals MeSH
- Check Tag
- History, 20th Century MeSH
- History, 21st Century MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Historical Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- RNA MeSH
- Telomerase MeSH
- telomerase RNA MeSH Browser
Parallel research on multiple model organisms shows that while some principles of telomere biology are conserved among all eukaryotic kingdoms, we also find some deviations that reflect different evolutionary paths and life strategies, which may have diversified after the establishment of telomerase as a primary mechanism for telomere maintenance. Much more than animals, plants have to cope with environmental stressors, including genotoxic factors, due to their sessile lifestyle. This is, in principle, made possible by an increased capacity and efficiency of the molecular systems ensuring maintenance of genome stability, as well as a higher tolerance to genome instability. Furthermore, plant ontogenesis differs from that of animals in which tissue differentiation and telomerase silencing occur during early embryonic development, and the "telomere clock" in somatic cells may act as a preventive measure against carcinogenesis. This does not happen in plants, where growth and ontogenesis occur through the serial division of apical meristems consisting of a small group of stem cells that generate a linear series of cells, which differentiate into an array of cell types that make a shoot and root. Flowers, as generative plant organs, initiate from the shoot apical meristem in mature plants which is incompatible with the human-like developmental telomere shortening. In this review, we discuss differences between human and plant telomere biology and the implications for aging, genome stability, and cell and organism survival. In particular, we provide a comprehensive comparative overview of telomere proteins acting in humans and in Arabidopsis thaliana model plant, and discuss distinct epigenetic features of telomeric chromatin in these species.
- Keywords
- Arabidopsis, aging, chromatin, epigenetics, human, review, telomerase, telomere,
- MeSH
- Chromatin metabolism MeSH
- Epigenesis, Genetic MeSH
- Humans MeSH
- Plants metabolism MeSH
- Cellular Senescence genetics MeSH
- Telomerase metabolism MeSH
- Telomere metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Chromatin MeSH
- Telomerase MeSH