Telomerase RNA processing: Implications for human health and disease

Abstract

Telomeres are composed of repetitive DNA sequences that are replenished by the enzyme telomerase to maintain the self-renewal capacity of stem cells. The RNA component of human telomerase (TERC) is the essential template for repeat addition by the telomerase reverse transcriptase (TERT), and also serves as a scaffold for several factors comprising the telomerase ribonucleoprotein (RNP). Unique features of TERC regulation and function have been informed not only through biochemical studies but also through human genetics. Disease-causing mutations impact TERC biogenesis at several levels including RNA transcription, posttranscriptional processing, folding, RNP assembly, and trafficking. Defects in TERC reduce telomerase activity and impair telomere maintenance, thereby causing a spectrum of degenerative diseases called telomere biology disorders (TBDs). Deciphering mechanisms of TERC dysregulation have led to a broader understanding of noncoding RNA biology, and more recently points to new therapeutic strategies for TBDs. In this review, we summarize over two decades of work revealing mechanisms of human telomerase RNA biogenesis, and how its disruption causes human diseases.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Update: Genetic Pathogenesis

“…TERT is the catalytic subunit of telomerase and contributes to the maintenance of telomere length ( 68 ). TERT rs2736100A is associated with shorter leukocyte telomere length ( 69 ).…”

Roles of telomeres and telomerase in age‑related renal diseases (Review)

“…Telomeres have been reported to serve an important role in the prognosis of patients with cancer, and the level of telomerase activity has been discovered to be maintained in 85% of malignancies, including RCC ( 12 ); however, how telomerase activity is maintained in RCC remains unknown. Human telomerase reverse transcriptase (TERT) is an active component of telomerase that is mainly responsible for its catalytic activity and is known to participate in the maintenance of stem cells, enhancement of DNA repair and promotion of late carcinogenesis ( 2 ).…”

“…When a telomere can shorten no more, several cellular signals such as DNA damage response, inflammatory and p53/p21 pathways are activated ( 11 ). The reverse transcriptase telomerase is an RNA-dependent DNA polymerase with two primary components: Reverse transcriptase and RNA ( 3 , 12 ). The RNA component of the telomerase sequence is complementary to the telomere template TTAGGG repeat, and the reverse transcriptase component helps to add six-base-pair units to the ends of chromosomes in repetitive cycles ( 2 , 12 ).…”

“…The reverse transcriptase telomerase is an RNA-dependent DNA polymerase with two primary components: Reverse transcriptase and RNA ( 3 , 12 ). The RNA component of the telomerase sequence is complementary to the telomere template TTAGGG repeat, and the reverse transcriptase component helps to add six-base-pair units to the ends of chromosomes in repetitive cycles ( 2 , 12 ). In this manner, telomerase helps to maintain telomere length (TL) in human stem cells, reproductive cells and cancer cells ( 13 ).…”

Long noncoding RNA LINC01291 promotes the aggressive properties of melanoma by functioning as a competing endogenous RNA for microRNA-625-5p and subsequently increasing IGF-1R expression

“…Increasing evidence suggests a relationship between lncRNAs and a variety of cellular processes [11][12][13]. Notably, several studies have indicated that lncRNAs exert cancer-suppressing or cancer-promoting activities and perform diverse functions in the oncogenesis and progression of human cancers [14][15][16]. With respect to melanoma, several lncRNAs are abnormally expressed and may exert regulatory effects on tumor-related processes [17][18][19].…”