Telomeres are primarily composed of DNA. However, it's crucial to understand that while the core structure of a telomere is repetitive DNA sequences, RNA plays a significant role in their function and dynamics.
The DNA Component of Telomeres
- A telomere is a protective cap at the end of a chromosome, consisting of repeating DNA sequences. These sequences prevent chromosome degradation and fusion. [Reference: A telomere is a region of repetitive DNA sequences at the end of a chromosome. Telomeres protect the ends of chromosomes from becoming frayed or tangled. Each time a cell divides, the telomeres become slightly shorter.]
- The length of telomeres is crucial for cell health and aging. Shortening telomeres are associated with aging and increased risk of certain diseases.
The RNA Component and its Interactions with Telomeres
- Telomeric RNA: Research shows that RNA molecules are transcribed from telomeric DNA sequences. [Reference: Here, we report that telomeric repeats are transcribed by DNA-dependent RNA polymerase II, which, in turn, interacts with the TRF1 shelterin protein.] These transcripts can form hybrids with telomeric DNA, creating DNA:RNA structures. [Reference: In addition, telomeric DNA:RNA hybrids were found in various human cancer cells, both telomerase-positive and ALT cancerous cells.]
- Telomerase, the enzyme responsible for maintaining telomere length, is an RNA-dependent DNA polymerase. It uses an RNA template to synthesize DNA, adding to the telomere. [Reference: Telomerase is an RNA-dependent DNA polymerase, meaning an enzyme that can make DNA using RNA as a template.]
- Telomeric DNA:RNA hybrids are found in various cell types, including cancer cells. Their presence affects telomere length and cellular senescence. [References: Telomeric RNA-DNA hybrids promote recombination-mediated elongation events that delay the onset of cellular senescence.; Detection of Telomeric DNA:RNA Hybrids Using TeloDRIP-qPCR; Telomeric DNA–RNA-hybrid G-quadruplex exists in environmental...] These hybrids are also implicated in the regulation of telomere maintenance, impacting processes like replication and recombination. [Reference: SKIV2L prevents telomere replication stress, independently of its helicase domain, and increases the stability of telomere DNA-RNA hybrids in G2.]
- Both DNA and RNA G-rich sequences within telomeres can form unique four-stranded structures (G-quadruplexes). [References: Human telomeric G‐quadruplex: structures of DNA and RNA ...; Human telomere, oncogenic promoter and 5′-UTR G ...] These structures have implications for telomere function and are potential targets for cancer therapeutics.
In summary, while telomeres are fundamentally composed of DNA, RNA plays a crucial supporting role through transcription, hybrid formation, and telomerase activity. Understanding both components is essential to fully grasping telomere biology and its implications in aging and disease.
