TERC (telomerase RNA component; HGNC:11727, NCBI Gene ID 7012) is a human locus mapped to chromosome band 3q26.2 that encodes the non-coding telomerase RNA component hTR (451 nucleotides; H/ACA box ribonucleoprotein scaffold). TERC provides the internal RNA template (5′-CUAACCCUAAC-3′) for TERT-mediated telomere synthesis and scaffolds assembly of the H/ACA dyskerin complex, working with TERT (Telomerase Reverse Transcriptase Catalytic Subunit Gene), Small Nucleolar RNA (H/ACA Box Domain Architecture), and Long Non-Coding RNAs. Encodes the 451-nucleotide non-coding RNA component of telomerase that supplies the template for TTAGGG telomeric DNA synthesis.
Genomic Organization & Cytogenetic Locus: Intronless single-exon non-coding RNA gene on chromosome 3q26.2 transcribed by RNA polymerase II into a nascent precursor whose 3-prime end is processed by the H/ACA snoRNP machinery and PARN poly(A)-specific ribonuclease into the mature 451-nucleotide vertebrate telomerase RNA (hTR).
Cellular & Tissue Expression Profile: Unlike TERT (which is tightly restricted to stem and germline cells), TERC is constitutively transcribed across most human somatic tissues as well as stem cells, so telomerase enzymatic activity is normally gated by the presence of the TERT protein catalytic subunit.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Folds into a conserved three-domain secondary structure: (1) a 5-prime core template/pseudoknot domain containing the 11-nucleotide sequence 5-prime-CUAACCCUAAC-3-prime that base-pairs with the chromosome 3-prime G-overhang and templates TTAGGG addition; (2) a CR4/CR5 three-way junction domain that directly stimulates TERT catalytic activity; and (3) a 3-prime H/ACA snoRNA-like domain with a CAB box that binds the dyskerin-NOP10-NHP2-GAR1 complex and TCAB1 for Cajal body localization.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Despite constitutive expression, TERC is strictly haploinsufficient in human stem cell compartments: heterozygous deletions or point mutations in the pseudoknot or template domains reduce telomerase activity by ~50%, causing progressive telomere shortening across generations (genetic anticipation) and autosomal dominant Dyskeratosis Congenita, bone marrow failure, and idiopathic pulmonary fibrosis.
Therapeutic & Clinical Pharmacology: The template region of TERC is the direct molecular binding target of the FDA-approved 13-mer lipid-conjugated N3-prime->P5-prime thio-phosphoramidate oligonucleotide imetelstat (Rytelo), which base-pairs with high affinity to the TERC template active site to competitively block telomerase in malignant myeloid clones.