DNA Transcription (Converting DNA to RNA)

Hey guys, it's Medicosus Perfection where medicine makes perfect sense. Let's continue our biochemistry playlist. In previous videos, we talked about DNA versus RNA, purines versus pyrimidines, nucleosides versus nucleotides. We talked about DNA replication and the story of the DNA polymerase. Today, we'll talk about transcription and the story of RNA polymerase. Today, we're cooking RNA from DNA via DNA polymerase enzyme. So, let's get started.

Please watch the videos in this playlist in order.

But first, let's answer the question of the previous video. If the mRNA codon is 5 prime AUG 3 prime, what's the correspondent complementary anticodon?

All right, I know this can get tricky, but here's the easy thing. I can read this this way or this way. It doesn't matter. Now, in real life, in your body, the DNA is synthesized from 5 prime to 3 prime, and the RNA is also synthesized from 5 prime to 3 prime. But just for playing with questions, I can read it anyway. So, I can say 5 prime A U G 3 prime, or I can say 3 prime G U A 5 prime.

I didn't change anything. I just read it backwards, like this.

And then what? We will have some base pairing. Base pairing is complementary. What I just wrote to you is the codon. Where do I find that? Always on the mRNA.

And this will pair with what? With the anticodon, which is found on the, remember, anticodon is on the tRNA.

Okay, let's try to figure out what the anticodon is.

The 3 prime will become 5 prime, and then the G will pair with C.

This U will pair with, oh, T.

Shut up. There is no such thing as thymine on RNA. It has to be A.

And the adenine will pair with uracil, and the 5 prime becomes 3 prime.

And the correct answer is B.

As in Bordetella pertussis, which causes whooping cough.

Remember the central dogma, when I copy my DNA, it's called replication.

When DNA becomes RNA, it's called transcription.

When the RNA becomes proteins, it's called translation.

Where is my DNA? It's in the nucleus.

Can it leave and go to the cytoplasm? No, it will get degraded and destroyed very quickly.

Your DNA is in the nucleus.

Transcription will convert it to RNA.

This RNA will take the info and go outside to the cytoplasm.

The RNA can leave, but DNA cannot.

Here is a quick review of your DNA. Please pause and review.

Remember that DNA has thymine, but RNA has uracil instead of thymine.

The purines include adenine and guanine. Pyrimidines include thymine, cytosine, and uracil.

Thymine is to DNA, what uracil is to RNA.

Never, ever confuse thymine with thiamine.

Thymine is a freaking nitrogenous base.

But thiamine is vitamin B1.

When you copy your DNA, it's called DNA replication.

Happens during the S phase of the cell cycle.

Let's open this origin of replication. Give me those replication forks.

And then we keep forking back and forth.

How do you unwind the double helix? Helicase.

Separate those two strands.

What's the name of the enzyme that will add new DNA nucleotides? DNA polymerase.

It will add those nucleotides in the 5 prime to 3 prime direction.

How do I prevent my DNA from coiling like this?

Just like your headphones in your backpack.

Well, in order to prevent this coiling, I need to prevent the formation of positive supercoils.

I.e., I need to add negative supercoils.

What's the name of the enzyme that will do this? Topoisomerase.

To prevent the entangling of your DNA, because the entangled DNA is absolutely useless.

So, what's the name of the enzyme that unwinds the double helix? Helicase.

Which one makes the primer, which is a short RNA molecule? Primase.

And which one will put the new DNA nucleotides? DNA polymerase.

And how do I prevent the supercoils? DNA topoisomerase.

All of this was discussed in details in previous videos.

Remember that DNA replication requires a primer, which is a short RNA, about 10 nucleotides or so.

Made by primase enzyme.

In the 5 prime to 3 prime direction.

And remember the difference between the leading strand and the lagging strand.

We're done with replication. Let's go to transcription.

Let's make RNA from DNA.

Who's going to put down new RNA nucleotides? RNA polymerase.

Here is my DNA.

That's the original strand.

We call it the coding strand.

And then when you replicate it, when you copy it, you give me a template strand.

The coding strand can also be known as the sense strand.

And the DNA template strand is the anti-sense, which is complementary to the sense.

What's the name of the beautiful enzymes that makes new DNA? It's called DNA polymerase.

After I have this DNA template.

Who's going to take it and make RNA from it? RNA polymerase.

Hashtag transcription.

And after that, you can use this mRNA to make lovely amino acids.

Bind them together by peptide bonds to make proteins.

Hashtag translation.

Today's video will focus on this step, transcription, which is converting the DNA template.

Not the coding strand, but the template strand.

It's going to be converted to RNA via transcription, via RNA polymerase.

Quick review on the different types of RNA.

Messenger RNA or mRNA is massive.

It's messenger because it carries the message from within the nucleus to outside of the nucleus.

What's the name of the enzyme that makes mRNA? DNA polymerase number 2.

Because the mRNA will leave the nucleus and go to the cytoplasm.

It carries the genetic info from the nucleus to the ribosomes.

mRNA is the only RNA that contains info that can be translated to proteins.

The first codon is AUG, which gives me methionine.

The last one is a stop codon, could be UAA, UGA, or UAG.

A stop codon will cause termination.

Next, ribosomal RNA or rRNA.

Ribosome on a smooth endoplasmic reticulum will make it no longer smooth.

It will become rough instead.

But what's a ribosome? It's rRNA and a bunch of proteins.

Where do we make rRNA, please? In the nucleolus.

Next, let's review our tRNA.

tRNA has the anticodon, which faces the codon of mRNA.

If I say that the mRNA goes 5 prime A U G and then 3 prime, it's the same thing as saying it goes 3 prime G U A 5 prime, which is written here.

Take this and then make it complementary to the anticodon on tRNA.

3 prime becomes 5 prime. G becomes C. U pairs with A, and A pairs with U.

And then the 5 prime becomes 3 prime.

This was the answer to the question of the previous video.

Now you get it.

The same concept applies.

I can take this and write it like this.

Just make sure to write your directions correctly.

How do we make this tRNA active? You charge it. You activate it.

You load it with amino acids at the 3 prime end, near the CCA pattern.

Who's going to load the amino acid onto the tRNA? A wonderful hard-working person in the warehouse.

Known as aminoacyl tRNA synthetase, which requires ATP.

And we will milk that ATP dry to yield two high-yield energy bonds.

Not just by converting it from ATP to ADP.

For that will only lead one high-energy bond.

No, I want to do it twice.

I want to go ATP to AMP from adenosine triphosphate to adenosine monophosphate.

Releasing two inorganic phosphate in the process, which releases two high-energy bonds.

This high energy is important because I will make a bond between the amino acid and the 3 prime end of the tRNA.

And this energy-rich bond will be used to supply energy to create a peptide bond between this amino acid and the subsequent amino acid.

Mnemonic time.

tRNA gets activated when amino acids are attached to its 3 prime end, thanks to aminoacyl tRNA synthetase.

Which requires ATP, two high-energy bonds.

Who made this wonderful tRNA? RNA polymerase 3.

3 prime end for the amino acid and 3 for the RNA polymerase.

And where was it synthesized? In the nucleus.

Which is the center of your cell.

Here's the coding strand replicated, you get the DNA template strand.

Transcribe it, you get RNA.

If you're talking mRNA, it's RNA polymerase 2.

If you're talking tRNA, it's RNA polymerase 3.

How about rRNA?

That will be RNA polymerase 1.

Because remember, my rRNA was the number one.

What do you mean?

It's the most abundant RNA.

Does DNA polymerase require a primer? Yes, it does.

Does RNA polymerase require a primer? No, it does not.

Why not, Medicosus?

Think about it.

If you're a mechanic, why would you hire a mechanic to fix your car?

You can just fix it yourself.

If you are a flipping neurosurgeon, why would you hire another neurosurgeon to perform the neurosurgery?

Why don't you get off of your ischial tuberosity and get to work?

By the same token, if you are RNA, why would you need a piece of RNA?

Known as the primer.

Oh, that doesn't make sense.

That's why RNA polymerase does not need a primer.

What's the first codon on the mRNA? It's AUG.

Which means it was TAC on the DNA template, which means it was ATG on the coding strand.

Notice that the first strand, which is the coding or sense, is very similar, if not identical, to the RNA.

With the only exception of, instead of saying thymine, I need to say uracil.

Because DNA versus RNA.

Other than that, they look identical.

So A was the first base. That's true.

And A was the first base on the coding strand.

What do you call the first base?

I call it plus one.

And then the next one, plus 2, plus 3, plus 4, plus 5, plus 6.

Anything before it, anything that is not part of my amino acids, will be given a negative number.

Which means there is no such thing as position zero.

Because we started at plus one, and anything before it is minus one.

Minus 2, minus 3, et cetera, et cetera, et cetera.

Until we reach the promoter.

The promoter is the site on the DNA template where the RNA polymerase binds.

It's called the TATA box.

Are you referring to the business tycoon from India?

No, I'm referring to thymine, adenine, thymine, adenine, thymine.

Et cetera, it's repeated.

TATA.

And just like how TATA promotes all kinds of business activities, the TATA box is the promoter.

It promotes RNA polymerase activity so that we can promote transcription from DNA to RNA.

So, who's the promoter? TATA box.

At which location? Negative 25.

On what strand? On the DNA template strand, also known as the anti-sense strand.

Remember in previous video, I've told you that mRNA is the messenger and it's massive.

rRNA is the ribosomal and it's rampant, I mean redundant, I mean abundant.

It's the number one.

Most abundant RNA in your body.

And then we have the transfer RNA, which is tiny.

But we need to rearrange them.

I need to start with rRNA because it's the number one most abundant.

Then mRNA because that's where you have the codon.

Hey, Medicosus, why don't you make the mRNA before the rRNA?

Why does this order matter?

Because what's the point of making mRNA so that we can translate it when you don't have a ribosome to make the translation happen?

Oh, that will be weird.

So that's why rRNA first, then mRNA, make the codon, and then pair it with the anticodon.

In this order.

And in this specific order, we will name our polymerases.

RNA polymerase 1 will make rRNA.

Then make the codon, which means RNA polymerase 2 is going to make mRNA.

And RNA polymerase 3 will synthesize tRNA.

Remember, the anticodon is on tRNA, anti-polymerase 3.

Where did we make rRNA, please?

In the nucleolus.

So RNA polymerase 1 is in the nucleolus.

However, 2 and 3 are in the nucleus because we make mRNA and tRNA in the nucleus.

Not in the nucleolus, which is in the nucleus.

Let's compare and contrast between DNA polymerase and RNA polymerase.

DNA polymerase makes DNA nucleotides during DNA replication.

But RNA polymerase makes RNA nucleotides during transcription.

Who needs a primer?

Only the DNA polymerase requires an RNA piece.

But if we're already making RNA, there is no need for another piece of RNA.

If you're a mechanic, you do not need to hire another mechanic.

Who has proofreading capabilities?

Only DNA polymerase.

RNA polymerase does not.

Because we live in a world of scarce resources which have alternative uses.

The body is trying to conserve and preserve your genetic code, which exists on your DNA.

Not on your RNA.

Who cares if RNA made mistakes?

We'll make another copy.

No one cares.

But if your genetic code gets screwed, you are screwed.

And I mean this as an understatement.

The central dogma gets more elaborate.

DNA, copy it, it's called replication.

Convert it to RNA, it's called transcription.

Which RNA? Heterogeneous RNA.

How about the mRNA?

We will do this through post-transcription modification. Only after post-transcription modification.

Do you get your lovely, desirable mRNA messenger from heterogeneous RNA?

And then the mRNA will leave the nucleus through the nuclear pores. It will go to the outside until it finds the ribosome.

And then translation happens.

Translation means synthesis of amino acids, and then you bind them together to make proteins.

Are we done yet?

No, the protein is not ready yet.

You need post-translational modification to get the desired end product.

Post-transcription modification will be the topic of the next video in this biochemistry playlist.

But before you go, let me give you a pearl for the pros.

Do you remember the mutations?

Yeah, we had point mutations, and we had frameshift mutations.

Point mutations could be silent mutations, missense, or nonsense.

Missense means misplaced. An amino acid got placed instead of the original correct amino acid.

Such as sickle cell disease.

Normally, there should be glutamic acid, but instead, we have valine.

That's not good.

This will lead to formation of something hydrophobic instead of hydrophilic protein.

Which will result in sickling of my red blood cells.

These sickle cells are dangerous for many reasons.

Number one, they cause hemolysis, which means destruction of the red blood cells.

And they clog my blood vessels, causing vaso-occlusive crises.

Which can damage my spleen and many other organs.

So, sickle cell disease is a missense mutation, which is a subtype of point mutation.

Which is a problem in one nucleotide in one codon.

However, there is another disease known as cystic fibrosis.

That's a frameshift mutation.

I shifted the frame.

Which resulted in loss of phenylalanine.

That's an amino acid.

Which will result in a defective chloride channel protein.

Of course, when the amino acid is abnormal, the protein will be abnormal.

When my chloride channel is abnormal, my secretions will be thick.

Such as my pancreatic secretions, causing fibrosis and cysts in my pancreas.

My bronchial secretions will be very thick, causing all kinds of lung infections.

These poor babies cough up tons of pus every single day.

And the unfortunate parents will have to change the position of the baby many times to get all the pus out every single day.

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Elimination, clearance, absorption, et cetera, download my general pharmacology course at medicosisperfectionis.com.

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