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Telomerase RNA component: The TERC gene provides instructions for making one component of an enzyme called telomerase.
1. Normal Function
The TERC gene provides instructions for making one component of an enzyme called telomerase. Telomerase maintains structures called telomeres, which are composed of repeated segments of DNA found at the ends of chromosomes. Telomeres protect chromosomes from abnormally sticking together or breaking down (degrading). In most cells, telomeres become progressively shorter as the cell divides. After a certain number of cell divisions, the telomeres become so short that they trigger the cell to stop dividing or to self-destruct (undergo apoptosis). Telomerase counteracts the shortening of telomeres by adding small repeated segments of DNA to the ends of chromosomes each time the cell divides.
In most types of cells, telomerase is either undetectable or active at very low levels. However, telomerase is highly active in cells that divide rapidly, such as cells that line the lungs and gastrointestinal tract, cells in bone marrow, and cells of the developing fetus. Telomerase allows these cells to divide many times without becoming damaged or undergoing apoptosis. Telomerase is also abnormally active in cancer cells, which grow and divide without control or order.
The telomerase enzyme consists of two major components that work together. The component produced from the TERC gene is known as hTR. The hTR component is an RNA molecule, a chemical cousin of DNA. It provides a template for creating the repeated sequence of DNA that telomerase adds to the ends of chromosomes. The other major component of telomerase, which is produced from a gene called TERT, is known as hTERT. The function of hTERT is to add the new DNA segment to chromosome ends.
2. Health Conditions Related to Genetic Changes
2.1. Idiopathic pulmonary fibrosis
Several mutations in the TERC gene have been identified in people with the progressive lung disease idiopathic pulmonary fibrosis. This condition causes scar tissue (fibrosis) to build up in the lungs, which makes the lungs unable to transport oxygen into the bloodstream effectively. Mutations in the TERC gene have been found in cases that run in families (familial pulmonary fibrosis) and, less commonly, in isolated (sporadic) cases. Some individuals with idiopathic pulmonary fibrosis due to TERC gene mutations have family members with other features of dyskeratosis congenita (described above), such as aplastic anemia or cancer.
Mutations in the TERC gene reduce or eliminate the function of telomerase, which allows telomeres to become abnormally short as cells divide. The shortened telomeres likely trigger cells that divide rapidly, such as cells that line the inside of the lungs, to stop dividing or to die prematurely. In people with idiopathic pulmonary fibrosis, shorter telomeres are associated with a more severe disease and a quicker decline in lung function. Additional research is needed to confirm how shortened telomeres contribute to the progressive scarring and lung damage characteristic of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis is a complex disease that is probably caused by a combination of genetic and environmental factors. Studies suggest that many affected people with TERC gene mutations may have also been exposed to environmental risk factors, such as cigarette smoke or certain kinds of dust or fumes. It is possible that mutations in the TERC gene increase a person's risk of developing idiopathic pulmonary fibrosis, and then exposure to certain environmental factors can trigger the disease.
2.2. Dyskeratosis congenita
At least 20 mutations in the TERC gene have been identified in people with dyskeratosis congenita. This disorder is characterized by changes in skin coloring (pigmentation), white patches inside the mouth (oral leukoplakia), and abnormally formed fingernails and toenails (nail dystrophy). People with dyskeratosis congenita have an increased risk of developing several life-threatening conditions, including cancer and a progressive lung disease called pulmonary fibrosis. Many affected individuals also develop a serious condition called aplastic anemia, also known as bone marrow failure, which occurs when the bone marrow does not produce enough new blood cells.
Some of the TERC gene mutations that cause dyskeratosis congenita result in an absent or unstable hTR molecule; others change the way hTR interacts with hTERT or other components of the telomerase enzyme.
TERC gene mutations lead to telomerase dysfunction, impaired maintenance of telomeres, and reduced telomere length. Cells that divide rapidly are especially vulnerable to the effects of shortened telomeres. As a result, people with dyskeratosis congenita may experience a variety of problems affecting quickly dividing cells in the body such as cells of the nail beds, hair follicles, skin, lining of the mouth (oral mucosa), and bone marrow.
Breakage and instability of chromosomes resulting from inadequate telomere maintenance may lead to genetic changes that allow cells to divide in an uncontrolled way, resulting in the development of cancer in some people with dyskeratosis congenita.
2.3. Other disorders
TERC gene mutations have also been found in people with isolated aplastic anemia, a form of bone marrow failure that occurs without the other physical features of dyskeratosis congenita. Researchers suggest that mutations affecting different parts of the telomerase enzyme may account for the absence of these features. Some believe that isolated aplastic anemia caused by TERC gene mutations may actually represent a late-onset form of dyskeratosis congenita in which physical features such as nail dystrophy are mild and may not be noticeable.
3. Other Names for This Gene
- small Cajal body-specific RNA 19
- telomerase RNA
- telomerase RNA component gene
This entry is adapted from https://medlineplus.gov/genetics/gene/terc
- Arish N, Petukhov D, Wallach-Dayan SB. The Role of Telomerase and Telomeres inInterstitial Lung Diseases: From Molecules to Clinical Implications. Int J MolSci. 2019 Jun 19;20(12). pii: E2996. doi: 10.3390/ijms20122996. Review.
- Armanios M. Syndromes of telomere shortening. Annu Rev Genomics Hum Genet.2009;10:45-61. doi: 10.1146/annurev-genom-082908-150046. Review.
- Armanios MY, Chen JJ, Cogan JD, Alder JK, Ingersoll RG, Markin C, Lawson WE,Xie M, Vulto I, Phillips JA 3rd, Lansdorp PM, Greider CW, Loyd JE. Telomerasemutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007 Mar 29;356(13):1317-26.
- Ballew BJ, Savage SA. Updates on the biology and management of dyskeratosiscongenita and related telomere biology disorders. Expert Rev Hematol. 2013Jun;6(3):327-37. doi: 10.1586/ehm.13.23. Review.
- Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009 Dec10;361(24):2353-65. doi: 10.1056/NEJMra0903373. Review.
- Calado RT. Telomeres and marrow failure. Hematology Am Soc Hematol EducProgram. 2009:338-43. doi: 10.1182/asheducation-2009.1.338. Review.
- Cronkhite JT, Xing C, Raghu G, Chin KM, Torres F, Rosenblatt RL, Garcia CK.Telomere shortening in familial and sporadic pulmonary fibrosis. Am J Respir CritCare Med. 2008 Oct 1;178(7):729-37. doi: 10.1164/rccm.200804-550OC.
- Dokal I. Dyskeratosis congenita. Hematology Am Soc Hematol Educ Program.2011;2011:480-6. doi: 10.1182/asheducation-2011.1.480. Review.
- Kirwan M, Dokal I. Dyskeratosis congenita, stem cells and telomeres. BiochimBiophys Acta. 2009 Apr;1792(4):371-9. doi: 10.1016/j.bbadis.2009.01.010.
- Marrone A, Sokhal P, Walne A, Beswick R, Kirwan M, Killick S, Williams M,Marsh J, Vulliamy T, Dokal I. Functional characterization of novel telomerase RNA(TERC) mutations in patients with diverse clinical and pathologicalpresentations. Haematologica. 2007 Aug;92(8):1013-20.
- Nishio N, Kojima S. Recent progress in dyskeratosis congenita. Int J Hematol. 2010 Oct;92(3):419-24. doi: 10.1007/s12185-010-0695-5.
- Tsakiri KD, Cronkhite JT, Kuan PJ, Xing C, Raghu G, Weissler JC, RosenblattRL, Shay JW, Garcia CK. Adult-onset pulmonary fibrosis caused by mutations intelomerase. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7552-7.
- Vulliamy TJ, Dokal I. Dyskeratosis congenita: the diverse clinicalpresentation of mutations in the telomerase complex. Biochimie. 2008Jan;90(1):122-30.
- Walne AJ, Dokal I. Advances in the understanding of dyskeratosis congenita. BrJ Haematol. 2009 Apr;145(2):164-72. doi: 10.1111/j.1365-2141.2009.07598.x.