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biology

Telomerase

Telomerase is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Telomerase rather than just read about it. In short: Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most eukaryotes.

Telomerase — main illustration
Telomerase — illustration

Key takeaways

  • Telomerase belongs to biology; place it in that map before memorising details.
  • Learn the definition first, then one example that makes the definition concrete.
  • Connect Telomerase to a quantity you can measure, compute or draw — that is where exam questions come from.
  • Reproduce the core statement of Telomerase from memory before moving on to harder problems.

Reference excerpt

Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most eukaryotes. Telomeres protect the end of the chromosome from DNA damage or from fusion with neighbouring chromosomes. The fruit fly Drosophila melanogaster lacks telomerase, but instead uses retrotransposons to maintain telomeres. Telomerase is a reverse transcriptase enzyme that carries its own RNA molecule (e.g., with the sequence 3′-CCCAAUCCC-5′ in Trypanosoma brucei) which is used as a template when it elongates telomeres. Telomerase is active in gametes and most cancer cells, but is normally absent in most somatic cells.

History The existence of a compensatory mechanism for telomere shortening was first found by Soviet biologist Alexey Olovnikov in 1973, who also suggested the telomere hypothesis of aging and the telomere's connections to cancer and perhaps some neurodegenerative diseases. Telomerase in the ciliate Tetrahymena was discovered by Carol W. Greider and Elizabeth Blackburn in 1984. Together with Jack W. Szostak, Greider and Blackburn were awarded the 2009 Nobel Prize in Physiology or Medicine for their discovery. Later the cryo-EM structure of telomerase was first reported in T. thermophila, to be followed a few years later by the cryo-EM structure of telomerase in humans. The role of telomeres and telomerase in cell aging and cancer was established by scientists at biotechnology company Geron with the cloning of the RNA and catalytic components of human telomerase and the development of a polymerase chain reaction (PCR) based assay for telomerase activity called the TRAP assay, which surveys telomerase activity in multiple types of cancer. The negative stain electron microscopy (EM) structures of human and Tetrahymena telomerases were characterized in 2013. Two years later, the first cryo-electron microscopy (cryo-EM) structure of telomerase holoenzyme (Tetrahymena) was determined. In 2018, the structure of human telomerase was determined through cryo-EM by UC Berkeley scientists.

Structure

The catalytic protein The main catalytic protein in telomerase is telomerase reverse transcriptase, 2627 amino acids long in humans. The protein consists of four conserved domains (RNA-Binding Domain (TRBD), fingers, palm and thumb), organized into a "right hand" ring configuration that shares common features with retroviral reverse transcriptases, viral RNA replicases and bacteriophage B-family DNA polymerases. TERT proteins from many eukaryotes have been sequenced.

The telomerase complex The full human telomerase complex (the holoenzyme) consists of: one copy each of telomerase RNA (TR or TERC, 452 nucleotides), TERT, and TCAB1, plus two copies of the H/ACA ribonucleoprotein subcomplex. The H/ACA subcomplex consists of two copies each of dyskerin (DKC1), NHP2, NOP10 and GAR1. Each copy of the H/ACA subcomplex binds to a hairpin structure on the telomerase RNA, a feature specific to vertebrates. There is also a histone H2A-H2B dimer wrapping around the telomeric DNA as it operates and its presence is essential for the functioning of the telomerase complex. The presence of TPP1 and POT1 is not detected in the cryo-EM study, but based on previous studies they should be attached to TERT's TEN domain in a way analogous to p50 and Teb1 of Tetrahymena. Previous experiments on catalytically active complex extracted from immortal cells indicated two molecules each of human TERT, telomerase RNA, and dyskerin (DKC1). For comparison, the Tetrahymena telomerase complex consists of: one copy each of TR (TER), TERT, p65 in the core; one copy of p50 (homolog of human TPP1) as the connection to the rest of the structure; one copy each of Teb1 (paralogous to human RPA70), Teb2, and Teb3 (altogether a RPA-like complex); and one copy each of p75, p45, p19 (a CST complex).

Mechanism

The shelterin protein TPP1 is both necessary and sufficient to recruit the telomerase enzyme to telomeres, and is the only shelterin protein in direct contact with telomerase. By using TERC, TERT can add a six-nucleotide repeating sequence, 5'-TTAGGG (in vertebrates; the sequence differs in other organisms) to the 3' strand of chromosomes. These TTAGGG repeats (with their various protein binding partners) are called telomeres. The template region of TERC is 3'-CAAUCCCAAUC-5'. Telomerase can bind the first few nucleotides of the template to the last telomere sequence on the chromosome, add a new telomere repeat (5'-GGTTAG-3') sequence, let go, realign the new 3'-end of telomere to the template, and repeat the process. Telomerase reverses telomere shortening.

Clinical implications

… excerpt ends here. Continue reading the full article.

Illustrations

Telomerase: Telomerase catalytic subunit TERT of Tribolium castaneum (Red flour beetle), bound to putative RNA template and telomeric DNA (PDB 3KYL)
Telomerase catalytic subunit TERT of Tribolium castaneum (Red flour beetle), bound to putative RNA template and telomeric DNA (PDB 3KYL)
Telomerase: A conceptual diagram showing the protein component of telomerase (TERT) in grey and the RNA component (TR) in yellow
A conceptual diagram showing the protein component of telomerase (TERT) in grey and the RNA component (TR) in yellow
Telomerase: An image illustrating how telomerase elongates telomere ends progressively
An image illustrating how telomerase elongates telomere ends progressively
Telomerase: Figure 4:A) Tumor cells expressing hTERT will actively degrade some of the protein and process for presenting. The major histocompatibility complex 1(MHC1), can then present the hTERT epitote. CD8- T cells that have antigen-specific T cell receptors against hTERT will then bind to the presented epitote. B) As a result of the antigenic binding, the T cells will release cytotoxins, which can be absorbed by the affected cell. C) These cytotoxins induce multiple proteases and result in apoptosis (or cell death).
Figure 4:A) Tumor cells expressing hTERT will actively degrade some of the protein and process for presenting. The major histocompatibility complex 1(MHC1), can then present the hTERT epitote. CD8- T cells that have antigen-specific T cell receptors against hTERT will then bind to the presented epitote. B) As a result of the antigenic binding, the T cells will release cytotoxins, which can be absorbed by the affected cell. C) These cytotoxins induce multiple proteases and result in apoptosis (or cell death).
Telomerase: Figure 5: A) Human telomerase RNA (hTR) is present in the cell and can be targeted. B) 2-5 anti-hTR oligonucleotides is a specialized antisense oligo that can bind to the telomerase RNA. C) Once bound, the 2-5 anti-hTR oligonucleotide recruits RNase L to the sequence. Once recruited, the RNase L creates a single cleavage in the RNA (D) and causes dissociation of the RNA sequence.
Figure 5: A) Human telomerase RNA (hTR) is present in the cell and can be targeted. B) 2-5 anti-hTR oligonucleotides is a specialized antisense oligo that can bind to the telomerase RNA. C) Once bound, the 2-5 anti-hTR oligonucleotide recruits RNase L to the sequence. Once recruited, the RNase L creates a single cleavage in the RNA (D) and causes dissociation of the RNA sequence.

Worked examples

Example 1 — a first encounter with Telomerase

Start with the simplest possible case. Write down what Telomerase claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Telomerase before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Telomerase ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Telomerase

In research
Telomerase appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry
Engineering practice reuses Telomerase in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom
Telomerase is common in secondary-school and first-year university syllabi. It links to neighbouring topics Aging-related enzymes, Anti-aging substances, DNA replication, so understanding it makes those chapters shorter.
In everyday life
Look for Telomerase outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Telomerase in 20 minutes

  1. Read the reference excerpt below once, without taking notes.
  2. Close the page and write down what Telomerase means in your own words.
  3. Compare your version with the excerpt and mark what you missed.
  4. Work through the three examples above with pen and paper.
  5. Explain Telomerase out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Telomerase in simple terms?

Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most eukaryotes.

Why does Telomerase matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Telomerase?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Telomerase.

Tags

  • Aging-related enzymes
  • Anti-aging substances
  • DNA replication
  • EC 2.7.7
  • Ribonucleoproteins
  • Senescence
  • Telomere-related proteins

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