chemistry

RNA-dependent RNA polymerase

RNA-dependent RNA polymerase is a chemistry 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 RNA-dependent RNA polymerase rather than just read about it. In short: RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template.

Key takeaways

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

Reference excerpt

RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to typical DNA-dependent RNA polymerases (DdRP), which all organisms use to catalyze the transcription of RNA from a DNA template. RdRp is an essential protein encoded in the genomes of most RNA-containing viruses that lack a DNA stage. Some eukaryotes also contain RdRps, which are involved in RNA interference and differ structurally from viral RdRps.

History Viral RdRps were discovered in the early 1960s from studies on Picornaviruses when it was observed that these viruses were not sensitive to actinomycin D, a drug that inhibits cellular DNA-directed RNA synthesis. This lack of sensitivity suggested the action of a virus-specific enzyme that could copy RNA from an RNA template.

Distribution

RdRps are highly conserved in viruses and are related to telomerase, though the reason for this was an ongoing question as of 2009. The similarity led to speculation that viral RdRps are ancestral to human telomerase. The most famous example of RdRp is in poliovirus. The viral genome is composed of RNA, which enters the cell through receptor-mediated endocytosis. From there, the RNA acts as a template for complementary RNA synthesis. The complementary strand acts as a template for the production of new viral genomes that are packaged and released from the cell ready to infect more host cells. The advantage of this method of replication is that no DNA stage complicates replication. The disadvantage is that no 'back-up' DNA copy is available. Many RdRps associate tightly with membranes making them difficult to study. The best-known RdRps are polioviral 3Dpol, vesicular stomatitis virus L, and hepatitis C virus NS5B protein. Many eukaryotes have RdRps that are involved in RNA interference: these amplify microRNAs and small temporal RNAs and produce double-stranded RNA using small interfering RNAs as primers. These RdRps are used in defense mechanisms and can be appropriated by RNA viruses. Their evolutionary history predates the divergence of major eukaryotic groups.

Replication RdRp differs from DNA-dependent RNA polymerase as it catalyzes RNA synthesis of strands complementary to a given RNA template. The RNA replication process is a four-step mechanism:

Nucleoside triphosphate (NTP) binding – initially, the RdRp presents with a vacant active site in which an NTP binds, complementary to the corresponding nucleotide on the template strand. Correct NTP binding causes the RdRp to undergo a conformational change. Active site closure – the conformational change, initiated by the correct NTP binding, results in the restriction of active site access and produces a catalytically competent state. Phosphodiester bond formation – two Mg2+ ions are present in the catalytically active state and arrange themselves around the newly synthesized RNA chain such that the substrate NTP undergoes a phosphatidyl transfer and forms a phosphodiester bond with the new chain. Without the use of these Mg2+ ions, the active site is no longer catalytically stable and the RdRp complex changes to an open conformation. Translocation – once the active site is open, the RNA template strand moves by one position through the RdRp protein complex and continues chain elongation by binding a new NTP, unless otherwise specified by the template. RNA synthesis can be performed by a primer-independent (de novo) or a primer-dependent mechanism that utilizes a viral protein genome-linked (VPg) primer. The de novo initiation consists in the addition of a NTP to the 3'-OH of the first initiating NTP. During the following elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product. Termination of the nascent RNA chain produced by RdRp is not completely known, however, RdRp termination is sequence-independent. One major drawback of RNA-dependent RNA polymerase replication is the transcription error rate. RdRps lack fidelity on the order of 104 nucleotides, which is thought to be a direct result of inadequate proofreading. This variation rate is favored in viral genomes as it allows for the pathogen to overcome host defenses trying to avoid infection, allowing for evolutionary growth.

Structure

Viral/prokaryotic RdRp, along with many single-subunit DdRp, employ a fold whose organization has been linked to the shape of a right hand with three subdomains termed fingers, palm, and thumb. Only the palm subdomain, composed of a four-stranded antiparallel beta sheet with two alpha helices, is well conserved. In RdRp, the palm subdomain comprises three well-conserved motifs (A, B, and C). Motif A (D-x(4,5)-D) and motif C (GDD) are spatially juxtaposed; the aspartic acid residues of these motifs are implied in the binding of Mg2+ and/or Mn2+. The asparagine residue of motif B is involved in selection of ribonucleoside triphosphates over dNTPs and, thus, determines whether RNA rather than DNA is synthesized. The domain organization and the 3D structure of the catalytic centre of a wide range of RdRps, even those with a low overall sequence homology, are conserved. The catalytic center is formed by several motifs containing conserved amino acid residues. Eukaryotic RNA interference requires a cellular RdRp (c RdRp). Unlike the "hand" polymerases, they resemble simplified multi-subunit DdRPs, specifically in the catalytic β/β' subunits, in that they use two sets of double-psi β-barrels in the active site. QDE1 (Q9Y7G6) in Neurospora crassa, which has both barrels in the same chain, is an example of such a c RdRp enzyme. Bacteriophage homologs of c RdRp, including the similarly single-chain DdRp yonO (O31945), appear to be closer to c RdRps than DdRPs are.

Viruses

Four superfamilies of viruses cover all RNA-containing viruses with no DNA stage:

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with RNA-dependent RNA polymerase

Start with the simplest possible case. Write down what RNA-dependent RNA polymerase claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, 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 RNA-dependent RNA polymerase 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 RNA-dependent RNA polymerase 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 RNA-dependent RNA polymerase

In research: RNA-dependent RNA polymerase appears in chemistry 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 RNA-dependent RNA polymerase 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: RNA-dependent RNA polymerase is common in secondary-school and first-year university syllabi. It links to neighbouring topics EC 2.7.7, Gene expression, RNA, so understanding it makes those chapters shorter.
In everyday life: Look for RNA-dependent RNA polymerase 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 RNA-dependent RNA polymerase in 20 minutes

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

Frequently asked questions

What is RNA-dependent RNA polymerase in simple terms?

Why does RNA-dependent RNA polymerase matter?

Because it connects several chemistry 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 RNA-dependent RNA polymerase?

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 RNA-dependent RNA polymerase.