Protein power: dna vs. rna

Deoxyribonucleic acid (DNA) and Ribonucleic acid (RNA) are perhaps the most important molecules in cell biology, responsible for the storage and reading of genetic information that underpins all life.

They are both linear polymers, consisting of sugars, phosphates and bases, but there are some key differences which separate the two1. These distinctions enable the two molecules to work together and fulfil their essential roles. Here, we look at 5 key differences between DNA and RNA.

Before we delve into the differences, we take a look at these two nucleic acids side-by-side. 

Protein Power: DNA vs. RNA

 A Comparison of the Helix and Base Structure of RNA and DNA

DNA vs. RNA – A Comparison Chart

Comparison DNA RNA
Full Name Deoxyribonucleic Acid  Ribonucleic Acid
Reactivity Due to its deoxyribose sugar, which contains one less oxygen-containing hydroxyl group, DNA is a more stable molecule than RNA, which is useful for a molecule which has the task of keeping genetic information safe. RNA, containing a ribose sugar, is more reactive than DNA and is not stable in alkaline conditions. RNA’s larger helical grooves mean it is more easily subject to attack by enzymes.
Ultraviolet (UV) Sensitivity DNA is vulnerable to damage by ultraviolet light.  RNA is more resistant to damage from UV light than DNA.

What are the key differences between DNA and RNA?

Function

DNA encodes all genetic information, and is the blueprint from which all biological life is created. And that’s only in the short-term.

In the long-term, DNA is a storage device, a biological flash drive that allows the blueprint of life to be passed between generations2. RNA functions as the reader that decodes this flash drive.

This reading process is multi-step and there are specialized RNAs for each of these steps. Below, we look in more detail at the three most important types of RNA. 

  • Messenger RNA (mRNA) copies portions of genetic code, a process called transcription, and transports these copies to ribosomes, which are the cellular factories that facilitate the production of proteins from this code.  
  • Transfer RNA (tRNA) is responsible for bringing amino acids, basic protein building blocks, to these protein factories, in response to the coded instructions introduced by the mRNA. This protein-building process is called translation. 
  • Finally, Ribosomal RNA (rRNA) is a component of the ribosome factory itself without which protein production would not occur3.

Both DNA and RNA are built with a sugar backbone, but whereas the sugar in DNA is called deoxyribose (left in image), the sugar in RNA is called simply ribose (right in image).

The ‘deoxy’ prefix denotes that, whilst RNA has two hydroxyl (-OH) groups attached to its carbon backbone, DNA has only one, and has a lone hydrogen atom attached instead.

RNA’s extra hydroxyl group proves useful in the process of converting genetic code into mRNAs that can be made into proteins, whilst the deoxyribose sugar gives DNA more stability4.

Protein Power: DNA vs. RNA

          The Chemical Structures of Deoxyribose (left) and Ribose (right) Sugars

The nitrogen bases in DNA are the basic units of genetic code, and their correct ordering and pairing is essential to biological function.

The four bases that make up this code are adenine (A), thymine (T), guanine (G) and cytosine (C). Bases pair off together in a double helix structure, these pairs being A and T, and C and G.

  RNA doesn’t contain thymine bases, replacing them with uracil bases (U), which pair to adenine1.

Whilst the ubiquity of Francis Crick and James Watson’s (or should that be Rosalind Franklin’s?) DNA double helix means that the two-stranded structure of DNA structure is common knowledge, RNA’s single stranded format is not as well known. RNA can form into double-stranded structures, such as during translation, when mRNA and tRNA molecules pair. DNA polymers are also much longer than RNA polymers; the 2.3m long human genome consists of 46 chromosomes, each of which is a single, long DNA molecule. RNA molecules, by comparison, are much shorter4.

Eukaryotic cells, including all animal and plant cells, house the great majority of their DNA in the nucleus, where it exists in a tightly compressed form, called a chromosome5.

This squeezed format means the DNA can be easily stored and transferred.

In addition to nuclear DNA, some DNA is present in energy-producing mitochondria, small organelles found free-floating in the cytoplasm, the area of the cell outside the nucleus. 

The Interplay between RNA and DNA Modifications: Back to the RNA World

An RNA/protein world (probably cellular) is widely accepted as a probable step in the early evolution of life. During subsequent life evolution various enzymes emerged that allowed some organisms to generate deoxyribonucleotides from ribonucleotide precursors and to synthesize DNA molecules using ancestral RNA genomes as templates.

Later on, once the DNA became the major repository of genetic information, cells and viruses had to develop new strategies to protect their DNA genomes against the aggressive chemical environment and/or destructive enzymes produced by competitors.

This was performed mainly by further modifying the DNA genomes after their synthesis through pre and postreplicative enzymatic processes, using enzymes, mostly methyltransferases and deaminases that were probably initially designated to modify primordial RNAs.

Relics of this ancient interplay between RNA and DNA modification in cells and viruses are still abundant in our modern ‘DNA-makes-RNA-makes-proteins’ world. Some enzymes are still able today to modify both DNA and RNA, demonstrating the versatility of the modification apparatus and testifying for the time when proteins of the late RNA world were recruited to work with DNA.

Here, we review what is known about these enzymes that were designated to synthesize DNA within the framework of a hypothetical cellular and viral co-evolution. From this analysis, DNA appears as just another type of (hyper)modified RNA polymer, specialized in storing the genetic inheritance of the living organisms.

For a long time DNA was viewed as the cornerstone of all biology, the mastermind of life, the aperiodic crystal whose existence had been wisely predicted by Schroedinger in his famous book “What is life?”.1 For Monod, a first meaningful DNA molecule appeared by chance in the primordial ocean and life began to emerge, just as Venus emerged from her shell.

2 In this scenario, RNA molecules appears only as a an intermediates used by DNA to perform its task, connecting informational content of its sequence to biologically active protein tools via passive “messenger” RNAs.

Why was DNA not directly translated to proteins then? Why do giant complex ribonucleoproteins (ribosomes) need RNA messenger, not “DNA messenger” to decode the genetic information?

From molecular designer's viewpoint, a DNA-based translation machinery would have been obviously more rational. However, living organisms are not rational machines, but historical products.

Nowadays, molecular biologists have completely revaluated the role of RNA in modern life and in life history: DNA is not the deux ex machina of the living world but, more simply, an RNA offspring and modern RNA molecules (cellular and viral) are now considered as vivid and fascinating relics of our distant past (the RNA world).3 The flow of information in present day ‘ribosome encoding organisms’,4 which has been enshrined in the central dogma ‘DNA-makes-RNA-makes proteins’,5 is itself the product of history.6 From an evolutionary point of view, one can identify several steps in this emerging pathway:7 first ‘RNA-makes-RNA’, second ‘RNA-makes-proteins’, third, “proteins make RNA” and finally “proteins-makes-DNA (from RNA)” (Fig. 1, boxes A-C).

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DNA thus appears as a by-product of the RNA world evolution and not the opposite.

As a matter of facts, in every cell examined so far, the deoxyribonucleotide precursors of DNA are produced by the enzymatic modification of RNA precursors (ribonucleotides) in which every 2'-hydroxyl group of ribose is reduced to a simple hydrogen and all the uracil bases are methylated to 5-methyl-uracil (thymine). In modern organisms, many cytidines and adenines in DNA are further deaminated to uracil or hypoxanthine, or modified to yield methylated derivatives and the enzymes involved in such postreplicative chemical alterations have many analogies with the homologous posttrancriptional base modification machinery in RNA (see below). Modern DNA thus appears as a heavily (hyper)modified RNA molecule.

In the early RNA world, the intrinsic chemical instability of RNA has probably limited the genome size, base modification can therefore have played very early a role in the evolution of the first living organisms toward more complexity, allowing the formation of longer proto-genomes and ribozymes.

The fight between parasites and their targets probably started early on (for instance between RNA viruses and RNA cells), also creating many opportunities for ribose and base modifications to be selected in the course of evolution.

The fine-tuning of ribozymes by base modification (a possibility presently unexplored in typical in vitro RNA world experiments) might also have been critical for the evolution of complex functions before the advent of modern proteins.

The aim of this chapter is to identify in our modern RNA/DNA/Protein world relics of biosynthetic and modification machineries that could testify for ancient processes and could shed light on the RNA to DNA transition.

Reduction of ribose to deoxyribose and transformation of dUMP to dTMP (to replace uracil in RNA by thymine in DNA) are performed in modern cells by sophisticated enzymes: ribonucleotide reductases (Fig. 1, box B and Fig. 2, box A) and thymidylate synthases (box B in Figs. 1 and 2).

The order of emergence of these two enzymes can be deduced from the fact that dUMP is the substrate of thymidylate synthase.

Thus ribonucleotide reductase should have originated first, followed by a polymerase that could synthesise U-containing DNA (U-DNA) using originally an RNA template (reverse transcription) and later on a U-DNA template. Thymidylate synthases originated later on, producing thymidine-containing DNA (T-DNA—Fig. 2, box B).

Ribonucleotide reductases and thymidylate synthases are encoded in all cellular genomes and in the genomes of many DNA viruses.

The complexity of the reaction catalyzed by the tetrahydrofolate-dependent thymidylate synthases (reviewed in chapter by Myllykallio et al in this volume), as well as the reductant–dependent ribonucleotide reductases—both types of enzymes requiring radical intermediate species—indicates that these reactions could not have been performed by ribozymes, or by polypeptides.7-9 Probably these reactions have been always performed by very sophisticated proteins. The first ribonucleotide reductases and thymidylate synthases were thus made by ancestral ribosomes containing both RNA and proteins and that were capable to perform already accurate translation. The RNA to DNA transition thus should have occurred in a complex cellular environment suitable for the production of these enzymes. This environment had to be elaborated enough to support the entire metabolism for the production of RNA precursors (rNTPs), including mechanisms for energy production. Hence, the cellular environment in which DNA finally emerged was not as “simple” as sometimes imagined, but was certainly populated by elaborated cells and viruses with an already complex metabolic network and well-organized membrane systems.7

Understanding SARS-CoV-2 and the drugs that might lessen its power

THE INTERCONNECTEDNESS of the modern world has been a boon for SARS-CoV-2. Without planes, trains and automobiles the virus would never have got this far, this fast.

Just a few months ago it took its first steps into a human host somewhere in or around Wuhan, in the Chinese province of Hubei.

As of this week it had caused over 120,000 diagnosed cases of covid-19, from Tromsø to Buenos Aires, Alberta to Auckland, with most infections continuing to go undiagnosed (see article).

But interconnectedness may be its downfall, too. Scientists around the world are focusing their attention on its genome and the 27 proteins that it is known to produce, seeking to deepen their understanding and find ways to stop it in its tracks.

The resulting plethora of activity has resulted in the posting of over 300 papers on MedRXiv, a repository for medical-research work that has not yet been formally peer-reviewed and published, since February 1st, and the depositing of hundreds of genome sequences in public databases.

(For more coverage of covid-19 see our coronavirus hub.)

The assault on the vaccine is not just taking place in the lab. As of February 28th China’s Clinical Trial Registry listed 105 trials of drugs and vaccines intended to combat SARS-CoV-2 either already recruiting patients or proposing to do so.

As of March 11th its American equivalent, the National Library of Medicine, listed 84.

This might seem premature, considering how recently the virus became known to science; is not drug development notoriously slow? But the reasonably well-understood basic biology of the virus makes it possible to work out which existing drugs have some chance of success, and that provides the basis for at least a little hope.

Even if a drug were only able to reduce mortality or sickness by a modest amount, it could make a great difference to the course of the disease.

As Wuhan learned, and parts of Italy are now learning, treating the severely ill in numbers for which no hospitals were designed puts an unbearable burden on health systems.

As Jeremy Farrar, the director of the Wellcome Trust, which funds research, puts it: “If you had a drug which reduced your time in hospital from 20 days to 15 days, that’s huge.”

What are the similarities between DNA and RNA

Nucleic acids form the building blocks of all living organisms. They are a group of complex compounds of linear chains of monomeric nucleotides where each of these nucleotides is made up of a phosphate backbone, sugar, and nitrogenous base.

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They are involved in the maintenance, replication, and expression of hereditary information. Two of the famous ones are DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). The DNA is awe-worthy, holding the key to heredity.

RNA is just as impressive, as it pretty much runs the show, with DNA as the main star. Together these molecules ensure that the DNA is replicated, the code is translated, expressed and that things go where they should go.

DNA and RNA are very similar to each other while they also manage to be different in just the right way.

Introducing DNA and RNA

Are you sufficiently freaked out about genetics; and by extension, this power couple (DNA and RNA), what they are, what they do and the implications of their activity? Most people get overwhelmed with genetics.

So fear not, here we are going to provide a simple introduction to the similarities between DNA and RNA and their differences, and then try to tie these to their functions and partnership. This way, you will understand the basics before you attempt to delve into the complicated and detailed roles of each.

Because of their intertwined fates in the form of the central dogma (Figure 1), we will discuss both the differences and similarities simultaneously.

Figure 1: Overview of the central dogma of molecular biology. Image Source: Wikimedia Commons

The Central Dogma

The central dogma explains the flow of the genetic code from DNA through all three types RNA to making protein. As you can tell from this, DNA and RNA both contain a chemical code central to the formation of proteins. Without the one, the flow of this information would break down, and that would be the end of life as we know it.

The DNA and RNA Structures

Figure 2: The structures of DNA and RNA, with the molecular structure of their bases. Image Source: Wikimedia Commons

Structurally these molecules are very similar with a few differences (Figure 2). They are both made up of monomers called nucleotides. Nucleotides simply refer to nitrogenous bases, pentose sugar together with the phosphate backbone.

Figure 3. Nucleic Acid sugars ribose and deoxyribose. Image Source: Wikimedia Commons

Both DNA and RNA have four nitrogenous bases each—three of which they share (Cytosine, Adenine, and Guanine) and one that differs between the two (RNA has Uracil while DNA has Thymine).

The pairing of these bases is the same between these nucleic acids; namely guanine bonds with cytosine while adenine bonds with thymine, or with uracil in the case of RNA. Secondly, DNA is double-stranded while RNA is single stranded.

Thirdly, DNA is more structurally stable compared to RNA. The comparably slight instability allows RNA to be flexible and more accessible and can thus fold into meaningful structures, a property that can be fully appreciated in the proteins RNA makes.

Lastly, they both contain a pentose sugar; DNA is a deoxyribose, a characteristic referring to the hydrogen where the hydroxyl group is on the ribose of the RNA molecule (figure 3).

One of the most significant similarities between DNA and RNA is that they both have a phosphate backbone to which the bases attach. Because of the phosphate group, this backbone is negatively charged—a quality many genetic techniques appreciate and exploit.

Birth, Death, and Maintenance of RNA and DNA

RNA is continuously made and degraded throughout the life of cells while DNA integrity is crucial. So, instead, DNA continually undergoes DNA replication to ensure this integrity across cells.

The body works in various ways to ensure the safety of this structure by continuously keeping all the DNA cleaving enzymes in check. RNA intrinsic function depends on its accessibility, flexibility, and dispensability.

Thus, all the “weaknesses” present in this structure are what make it so important and vital to the success of DNA duties.

DNA and RNA Dependency, Regeneration and Replication

Due to the fragile nature of DNA, it resides within the nucleus where it is protected. DNA and RNA form the perfect partners in crime whose primary functions are to ensure gene expression and protein synthesis. RNA is found both in the nucleus and the cytoplasm, this way it can shuttle the DNA message from the nucleus to the targets.

RNA is not as fragile and as such can afford to mile around in ways DNA can’t. Because RNA has to move around so much and performs many functions in the synthesis of proteins, different types of RNA are synthesized, and there is a division of labor between them.

The three different types of RNA associated with the central dogma are messenger RNA (mRNA), transporter RNA (tRNA) and ribosomal RNA (rRNA).

DNA is self-sufficient, providing a template for its DNA replication and the information for RNA synthesis. The antiparallel nature of DNA makes it such that each strand (antiparallel and parallel) can serve as a template and with the aid of numerous proteins can self-duplicate. This is especially integral because when you make new cells they all need to be copies of each other.

Location, Location, Location

DNA is a fragile molecule that forms the basis of most, if not all, biological function. As stated before, because of its fragile nature it resides within the nucleus where it is protected.

Some DNA is also found in organelles such as mitochondria and chloroplast—think ENDOSYMBIOTIC THEORY to make sense of this (a story for another day).

Since DNA needs to maintain its integrity, it is of utmost important to ensure that it is exposed to minimal danger and to ensure this it is confined to the nucleus where several proteins are entrusted with its safety while RNA ensures that the functions of DNA are fulfilled.

Uracil and Thymine, Which One is Better?

Figure 5: Chemical structure of Thymine. Image Source: Wikimedia Commons Figure 6: Chemical structure of Uracil. Image Source: Wikimedia Commons

Uracil and Thymine serve a similar in form and function with one important difference—the methyl group (Figure 5 and Figure 6).

Thymine is energetically taxing to make while Uracil can be easily assembled through deamination of cytosine. Uracil is more flighty and friendly, occasionally pairing with any other base, including itself. Thus for the integrity of DNA, uracil becomes an unwise choice—hence thymine.

So why is it OK for RNA to use uracil, you ask? Well, due to its disposable nature, RNA is not meant to be made for longevity; therefore, cheaper material during its assemblage can be used.

To Be Double-Stranded or Single-Stranded is the Question

Why is DNA double-stranded? And if this is a good idea why doesn’t RNA do it too? Once again, the integrity of DNA is so important that pretty much everything about it is about keeping it safe. The order and assemblage of the nitrogenous bases are what the genetic code is about, everything around it is—once again—about keeping it safe.

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Therefore, as you can guess, it would not be wise to leave this precious code exposed. One way of making sure it is concealed then is by having complementary ones strategically facing each other, the adjacent ones held together by the backbone and then proceeding to pack tightly into chromosomes.

This way all the harsh dangers in the nucleus are not able to access and thus mutate the genetic code.

The presence of two strands also provides the proof against which the other strand can be checked and fixed.

So why isn’t RNA doing the same thing? Well, once again RNA doesn’t hang around long enough to warranty such safety precautions, it would be a waste of energy and space—and as we all know, energy (ATP) is a precious commodity in the molecular function of the cell (another story for another day). In addition to this, RNA serves as a template against which the code for protein can be carried, therefore, exposed bases are readily available for this function.

What are the Differences Between Deoxyribose and Oxyribose Sugar?

The absence of the one Oxygen reduces the reactivity of DNA, ensuring that it does not get involved where it should not, thereby reducing the risk of being broken down.

However, given that the majority, if not all, of RNA functions, depend on it being busy and hyper-reactive, it is just as well then that it keeps that Oxygen to ensure maximum functionality.

You can think of messenger RNA as an ON, and OFF switch of gene expression and the presence/absence of this Oxygen is central to this function.

Recap and Conclusion

Hopefully this information did not make your head spin. If it did, below you will find a short recap. Both molecules contain a phosphate backbone and are made up of nucleotides. DNA carries all the information needed for DNA replication and transfer new information to new cells.

This information is also needed to make proteins the body needs for various purposes including regulation of DNA replication. RNA is transcribed from the DNA to make these proteins (the central dogma, Figure 1).

RNA is transcribed and processed within the nucleus, it then moves through the nuclear pores for protein translation in the cytoplasm. In this sense, DNA and RNA are the perfect partners in crime. What DNA can’t do, RNA can and what DNA can do RNA can’t.

What results from this perfect partnership is that the single-stranded RNA can be made from the double stranded DNA. The nucleus confined DNA can send its message to the rest of the cell with the aid of the RNA, which moves around freely through the cell.

The “dangers” faced by the RNA means it might or does need to be recreated and continuously destroyed, DNA provides the platform for the rebirth of this molecule. By all accounts, DNA and RNA differ in just the right amount while they are also similar just right and hopefully this point was made plenty clear here.

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Protein Power: DNA vs. RNA

A couple of weeks ago, in the episode called The Secret Life of Genes, I talked about the fascinating lives of genes. Our friend Addy the nucleotide had a job he loved, helping transcribe DNA into messenger RNA, (or mRNA), the code that tells the cell how to build proteins.

This week, we’ll take a closer look at how that works by looking at the difference between DNA and RNA.;

It All Starts with Genes

As I mentioned in my episode on The Human Genome, each of your genes is a little section of DNA that contains the instructions for creating a protein. DNA is made up of 4 different kinds of nucleotides: Guanine, Adenine, Thiamine, and Cytosine. Since those names don’t exactly roll off the tongue, we usually just abbreviate them as G, A, T, and C. 

The rungs of the DNA ladder are formed when associated bases on each strand stick together. Guanine binds to Cytosine and Adenine binds to Thiamine. Each of these ladder rungs is called a “base pair” because they are made of a pair of nucleotide bases.

When your cell wants to make a protein, it sends an enzyme, called RNA polymerase II to make a copy of your DNA (there are other varieties or RNA Polymerase that make other things, but we won’t discuss them today).

What’s in a Name?

Anytime you see something biological ending in “ase,” it usually means that it is an enzyme. An enzyme is a special kind of protein that catalyses a chemical reaction. This means it allows the reaction to occur, or helps to speed it up. 

The “polymer” part means that this particular enzyme catalyses a reaction that results in making a polymer. You’ve probably heard the world polymer before. It means something big made of a bunch of small somethings stuck together. Since this is RNA polymerase, the something big is an RNA molecule and the small somethings are nucleotides. 

So putting that all together, what RNA polymerase does is catalyze the reaction where a bunch of nucleotides are stuck together to form an RNA molecule.

Running with RNA

RNA polymerase II does its work by running along the DNA molecule and taking advantage of the base pairing feature of DNA. Every time it sees a Guanine nucleotide, it sticks a Cytosine to it, and vice versa.

When it sees a Thymine nucleotide, it sticks an Adenine to it.

And just when you thought things might be making a little bit of sense, when it sees an Adenine, instead of sticking a Thymine to it, it slips in a Uracil nucleotide. 

Why in the world does it do that? Let’s see if we can figure it out by looking at the difference between DNA and RNA.

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