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In yeast, five gene products are required for telomerase activity in vivo: Est2p (the catalytic reverse transcriptase subunit), TLC1 (the template RNA), Est1p, Est3p and Cdc13p. Mutations in any of these five genes lead to progressive telomere shortening, the so-called ever shorter telomeres (EST) phenotype, followed by cell death. CDC13 is the only essential gene among the EST genes. Est2p and TLC1 form the catalytic core of telomerase, while Est1p, Est3p and Cdc13p which are dispensable for in vitro telomerase catalytic activity, play regulatory roles (6, 8, 10, 14, 16 and references therein). Cdc13p, a single stranded DNA binding protein required for telomere maintenance and elongation, binds to Est1p and this interaction is necessary for recruiting telomerase to the chromosomal ends. Est1p, Est2p and Est3p all bind to the TLC1 RNA template and Est1p also binds to 3' ends of single stranded DNA. Est1p forms a stable complex with TLC1 in the absence of Est2p or Est3p while association of Est3p with the enzyme requires an intact catalytic core. Est1p and Est3p are stable components of the telomerase holoenzyme (14).TLC1 is the template for the synthesis of the single stranded chromosome end synthesis; it also provides a scaffold for the assembly of the telomerase ribonucleoprotein complex and it modulates enzyme activity (7). TLC1 was identified from a screen for telomeric silencing defects (1). In S. cerevisiae, the TLC1 RNA is a polyadenylated, 1.3 kb transcript produced by RNA polymerase II. An increase in the amount of polyA+ TLC1 transcript is observed between the G1 and S phases of the cell cycle, suggesting that TLC1 RNA levels are regulated in a cell-cycle dependent manner (8).Analysis of the secondary structure of the TLC1 RNA has provided insights into the RNA-protein interactions that are necessary for the assembly and activity of the telomerase complex. A base-paired element immediately adjacent to the template, provides a template boundary to terminate each cycle of reverse transcription (5) and three stem-loop structures provide protein binding sites for the Est2p, Est1p telomerase subunits and for the Ku heterodimer (Yku70p-Yku80p) (9, 12, 13). Binding of Est1p with TLC1 is proposed to provide a bridge between the catalytic Est2p and the telomere-bound Cdc13p, thereby mediating an essential step in telomere replication (9, 12, 13). Interaction of TLC1 RNA with the Ku dimer promotes the addition of telomeres to broken chromosome ends, thereby repairing damaged DNA by capping the broken end with telomeric DNA (13, 15). The TLC1 RNA also contains an Sm binding site near its 3' end and is bound by the heteroheptameric Sm ring complex, which also binds to many of the splicesomal snRNAs and is encoded by SMB1, SMD1, SMD2, SMD3, SME1, SMX3 and SMX2 (18). It has been proposed that the Sm proteins play a role in the intracellular transport, assembly and maturation of the telomerase RNP complex. Approximately 40% of the length of the TLC1 RNA, including the template region and the Est2p and Est1p binding sites, is required for telomerase function (19).In humans, telomere length is linked to aging and cancer: in human germline cells telomeres are long, whereas in cells of somatic tissues, telomerase activity is absent and the telomeres are short. Upon sufficient shortening, the somatic cells stop dividing and become senescent. Inappropriate telomerase activity is detected in most malignant tumors, and the genes required for telomerase activity are potential targets for cancer therapy (4, 8).

Human orthologs for four of the telomerase subunits are known. Est2p, the telomerase reverse transcriptase catalytic enzyme, is similar to TERT (OMIM), TLC1, the template RNA is similar to TERC/hTR (OMIM), while Cdc13p shares sequence similarity with human POT1 (OMIM) (11, 10). There are three Est1p like proteins in humans, although only hEST1A and hEST1B have been shown to be associated with the telomerase (17). A human ortholog for EST3 hasn't been identified. Mutations in TERT (OMIM) and TERC/hTR (OMIM) cause short telomeres and congenital aplastic anemia (OMIM, 11).", "date_edited": "2007-06-07"}, "literature_overview": {"primary_count": 149, "additional_count": 117, "review_count": 78, "go_count": 6, "phenotype_count": 13, "disease_count": 0, "interaction_count": 55, "regulation_count": 0, "ptm_count": 0, "funComplement_count": 0, "htp_count": 1, "total_count": 361}, "disease_overview": {"manual_disease_terms": [], "htp_disease_terms": [], "computational_annotation_count": 0, "date_last_reviewed": null}, "ecnumbers": [], "URS_ID": "URS0000348061", "main_strain": "S288C", "regulation_overview": {"regulator_count": 0, "target_count": 0}, "reference_mapping": {"600829": 1, "384760": 2, "354179": 3, "610800": 4, "505263": 5, "583609": 6, "501592": 7, "632043": 8, "540296": 9, "540136": 10, "532875": 11, "556671": 12, "549414": 13, "551046": 14, "616283": 15, "548617": 16, "545077": 17, "598485": 18, "561950": 19}, "history": [{"category": "Name", "history_type": "LSP", "note": "Name: TER1", "date_created": "2010-02-16", "references": []}, {"category": "Annotation change", "history_type": "SEQUENCE", "note": "Annotation change: The feature_type annotation of TLC1 was changed from ncRNA to telomerase_RNA_gene (SO:0001643) as part of SGD's genome annotation revision R64.2.", "date_created": "2014-11-18", "references": []}], "complexes": [{"format_name": "CPX-3298", "display_name": "Telomerase holoenzyme complex"}]}, tabs: {"id": 1285626, "protein_tab": false, "interaction_tab": true, "summary_tab": true, "go_tab": true, "sequence_section": true, "expression_tab": false, "phenotype_tab": true, "literature_tab": true, "wiki_tab": false, "regulation_tab": true, "sequence_tab": true, "history_tab": true, "homology_tab": false, "disease_tab": false} }; TLC1 | SGD

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TLC1 / YNCB0010W Overview

Standard Name
TLC1 1
Systematic Name
YNCB0010W
SGD ID
SGD:S000006657
Aliases
TER1
Feature Type
telomerase RNA gene
Description
RNA template component of telomerase; flexible scaffold that tethers telomerase holoenzyme protein subunits to the complex; contains template sequence that Est2p uses to add irregular repeats of TG(1-3) residues onto a DNA end; promoter regulated by the cell cycle dependent transcriptional activators Swi4p/Swi6p and Mbp1p/Swi6p 1 2 3
Name Description
TeLomerase Component 1
RNAcentral ID
URS0000348061
Secondary Structure
Comparative Info
Sequence Details

Sequence

The S. cerevisiae Reference Genome sequence is derived from laboratory strain S288C. Download DNA or protein sequence, view genomic context and coordinates. Click "Sequence Details" to view all sequence information for this locus, including that for other strains.

Analyze Sequence

S288C only

BLASTN | Design Primers | Restriction Fragment Map | Restriction Fragment Sizes

S288C vs. other species

BLASTN vs. fungi

Alleles

Curated mutant alleles for the specified gene, listed alphabetically. Click on the allele name to open the allele page. Click "SGD search" to view all alleles in search results.

View all TLC1 alleles in SGD search

Gene Ontology Details

Gene Ontology

GO Annotations consist of four mandatory components: a gene product, a term from one of the three Gene Ontology (GO) controlled vocabularies (Molecular Function, Biological Process, and Cellular Component), a reference, and an evidence code. SGD has manually curated and high-throughput GO Annotations, both derived from the literature, as well as computational, or predicted, annotations. Click "Gene Ontology Details" to view all GO information and evidence for this locus as well as biological processes it shares with other genes.

Molecular Function

Manually Curated

Biological Process

Manually Curated

Cellular Component

Manually Curated

Complex

Macromolecular complex annotations are imported from the Complex Portal. These annotations have been derived from physical molecular interaction evidence extracted from the literature and cross-referenced in the entry, or by curator inference from information on homologs in closely related species or by inference from scientific background.

Phenotype Details

Phenotype

Phenotype annotations for a gene are curated single mutant phenotypes that require an observable (e.g., "cell shape"), a qualifier (e.g., "abnormal"), a mutant type (e.g., null), strain background, and a reference. In addition, annotations are classified as classical genetics or high-throughput (e.g., large scale survey, systematic mutation set). Whenever possible, allele information and additional details are provided. Click "Phenotype Details" to view all phenotype annotations and evidence for this locus as well as phenotypes it shares with other genes.

Interaction Details

Interaction

Interaction annotations are curated by BioGRID and include physical or genetic interactions observed between at least two genes. An interaction annotation is composed of the interaction type, name of the interactor, assay type (e.g., Two-Hybrid), annotation type (e.g., manual or high-throughput), and a reference, as well as other experimental details. Click "Interaction Details" to view all interaction annotations and evidence for this locus, including an interaction visualization.

523 total interactions for 434 unique genes

Physical Interactions

  • Affinity Capture-RNA: 43
  • Affinity Capture-Western: 1
  • Co-purification: 2

Genetic Interactions

  • Dosage Growth Defect: 1
  • Dosage Rescue: 4
  • Negative Genetic: 103
  • Phenotypic Enhancement: 18
  • Phenotypic Suppression: 30
  • Positive Genetic: 244
  • Synthetic Growth Defect: 22
  • Synthetic Lethality: 5
  • Synthetic Rescue: 50
Regulation Details

Regulation

The number of putative Regulators (genes that regulate it) and Targets (genes it regulates) for the given locus, based on experimental evidence. This evidence includes data generated through high-throughput techniques. Click "Regulation Details" to view all regulation annotations, shared GO enrichment among regulation Targets, and a regulator/target diagram for the locus.

No regulation data available.

Summary Paragraph

A summary of the locus, written by SGD Biocurators following a thorough review of the literature. Links to gene names and curated GO terms are included within the Summary Paragraphs.

Last Updated: 2007-06-07

Literature Details

Literature

All manually curated literature for the specified gene, organized into topics according to their relevance to the gene (Primary Literature, Additional Literature, or Review). Click "Literature Details" to view all literature information for this locus, including shared literature between genes.

Primary
149
Additional
117
Reviews
78

Resources

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