Translation (mRNA to protein)

- [Voiceover] So we already know that chromosomes are made up of really long strands of DNA all wound up into themselves, so something like, well I'm just kind of drawing it as a random long strand of DNA all wound up in itself. And on that strand, you have sequences which we call genes, so that might be one gene right over there, this might be another gene, that might be a gene right over there. And each of those genes can code for specific polypeptides or specific proteins. And the key question is, is how do you go from the information encoded in these genes, encoded as sequences of DNA, how do you go from that? How do you go from the gene, which is encoded in DNA, how do you go from that to protein? Which is made up of polypeptides, which are made up of amino acids. And this is often called the central dogma of biology, but we already saw in the video of transcription, that the first step is to go from the gene to messenger RNA, that the RNA, the messenger RNA, you can use as a transcript, we have rewritten the information now as RNA. And then the next step which we're gonna dive into in this video is going from that message RNA to protein, and this process is called translation, because we're literally translating that information into a polypeptide sequence. And you can see a little bit visually here, this is all review, we covered a lot of this in the video on transcription and the overview video on transcription and translation, is if you look at a eukaryotic cell and the bacteria in a prokaryotic cell, it's analogous, you just don't have the nuclear membrane, and you're not gonna do the processing step that I'm gonna talk about in a little bit and we went in detail on the video on transcription. But you start with the DNA, you have your RNA polymerase as the main actor that's able to transcribe the RNA from that. If we're talking about a eukaryotic cell, what you end up with we wouldn't call mRNA we would call pre-mRNA, pre-mRNA, which then needs to be processed, the introns need to be taken out, we add a cap and a tail here, and if we're talking about a eukaryotic cell, we then formally call that mRNA, and then it can travel, and this is where we get into the translation step. It can travel to a ribosome, which is where it will be translated into a polypeptide sequence. And you see the analogous thing happening here in this bacterial, or this prokaryotic cell right over here, except you don't see the nuclear membrane, because it's prokaryotic, and you don't see that processing step, so you could just consider this straight, this is mRNA right over there. So the questions are well how does this thing happen? And what even is a ribosome? So let's zoom in a little bit on a ribosome right over here, and there's a couple of interesting actors. One, as you can imagine, is the ribosome itself, and it is made up of proteins, proteins plus ribosomal RNA. So in the video on transcription, we're already familiar with messenger RNA and we often view RNA like DNA as primarily encoding information, it's acting as a transcript for a gene, but it doesn't have to only encode information. It can also, so it's proteins plus, it's not a 'T' there, this is a plus. It can also provide a functional structural role, which it does in ribosomal RNA. And this big, you know, this looks like a an oversized hamburger bun or something right over here, this is super oversimplification of what a ribosome looks like and I encourage you to do a web search for image searches for ribosomes, and then you can get more appreciation of how how beautiful these structures are, and how intricate they actually are. So this is the site, and you can broadly think of the ribosome as having this, you know, this is the top bun, and the bottom bun. And it's going to travel along the mRNA from the five prime end, to the three prime end, reading it, and taking that information, and turning it into a sequence of amino acids. So how does that actually happen? Well, each, each of these three, every three nucleotides, every three nucleotides there, we call that a codon, so that's a codon, this is, let me do this in a color that is visible on both white and black. So these next three nucleotides is a codon, this is a codon, this is a codon, and what's actually the information is actually encoded in the nitrogenous bases. So this first codon right over here, we see it's AUG, so the nitrogenous bases are adenine, uracil and guanine. And this has, this codon, it codes for the amino acid methionine, but this is also, this is a good one to know, AUG, let me write it over here. AUG is know as the start codon. Start codon. This is where the ribosome will initially attach to start translating that messenger RNA, and so we, the way this drawing is, that we are just starting to translate this messenger RNA. So how does that actually happen? How do we get from these three letter sequences to specific amino acids? Well let's think about it, how many, how many possible three letter sequences are there? Well, there are, there are four possible nitrogenous bases there, so there's four possible, so if you, if you have a codon, and it has three places, there's four possible things that could be in the first place. There's four possible things that could be in the second place, and there's four possible things that could be in the third place. So there are 64 possible permutations. 4 times 4 times 4. Permutations, so you can think of it, there's 64 different codons, different ways of arranging the A, the U and the G. And that's good, because there are many amino acids, and this is actually overkill, because there's actually 22 standard amino acids, 22 standard, amino, amino acids, and 21 that are typically found in eukaryotic cells. So we have more than enough, more than enough permutations to cover the different amino acids. And it's not hard to find tables that will actually show us what the different sequences, what they actually code for. So you can see here, you can take the first letter, the second letter and the third letter, figure, look at the different sequences, and you can say, okay, look at that. AUG, adenine, uracil, guanine. That codes for methanine. Right over here. You could do that with any of them, you could say cytosine, uracil, uracil, that codes for leucine. And you can see that it's not just one amino acid per codon, but here you have four codons all code for, all code for leucine. And so it turns out that 61 of the codons, let me write this down. So 61 of the codons, of the possible 64, code for amino acids, amino acids, and three play a role that essentially tells the the ribosome to stop, three codons, three codons are stop codons, and you can see them right over here. UAA, UAG, UGA, that's how the ribosome knows to stop translating. So AUG, that's a start codon, and it codes for methionine. So that lets you know that these polypeptide chains are going to start with methionine, and then these characters tell it where to stop. But how do, how does the amino acid actually get, how do they all get tied up together to form this polypeptide? And how do they get matched up, how do they actually get matched up with the appropriate codon? And that's where we have another RNA based actor, and this is tRNA. So tRNA, the t stands for transfer, transfer RNA. There's a bunch of different tRNAs that each combined to specific amino acids, and on parts of those tRNA, they have what are called anti-codons. That pair with the appropriate codon. So this tRNA, and that's not what it looks like, I'll show you in a second what it looks like. That's a tRNA molecule, tRNA, at one end of the molecule, it's binding to the appropriate amino acid, methionine, right over here. And then at the other end of the molecule, though that's in the middle of the tRNA actual chain, you have your anticodon. And your anticodon matches up to the appropriate codon. And so this is how they bump into each other the right way and the ribosomes going to facilitate it, that the AUG is going to be associated with the methionine. And if we look at what tRNA actually looks like, and this is still just a visualization. So this is a strand of tRNA, you get a sense of, okay, it's a sequence of RNA right over here, this it's, I guess you could say, you could think of it, it's two dimensional structure. But then it wraps around itself to form this fairly complex molecule. And the anticodon, which is right here, it's kind of in the middle of the sequence, it forms the basis for this end of the molecule, that's the part that's gonna pair with the codon on the mRNA, and then at the other end of the molecule, at the other end of the molecule is where you actually bind to the appropriate amino acid. So I know what you're thinking, alright, I see that the ribosome, it knows where to start, it starts at the start codon. I see how the appropriate tRNA can bring the appropriate amino acid, but how does the chain actually form? And you can view this in three steps, and associated with those three steps are three sites on the ribosome. And the three sites, we call this the A-site, you're not gonna be able to see it if I write it in black. A, or yellow, alright, let me write it in blue. So that is the A-site. This is the P-site, and this is the E-site. And I'll talk in a second why we call them A, P and E. So the A-site is where the appropriate tRNA initially bounds, the tRNA that's bound to an amino acid. And so you can see, we're starting the translation process, the next thing that's going to happen is another tRNA, the one that is, that matches, that has an anticodon that matches the UAU, that's going to bond over here on the A-site, and it's bringing the appropriate amino acid with it, it's bringing the tyrosine with it. So why is that called the A-site? Well A stands for aminoacyl. An easy way to remember it it's the tRNA, it's the place where the tRNA that's bound to the amino acid, just one amino acid is going to bind on the ribosome. And so once that happens, once this character comes here, let me draw that. Once this character comes right over here, it's gonna be AUA, and it's bound to the tyrosine. Well then you could have a peptide bond form between the two amino acids, and the ribosome, and the ribosome itself can move to the right. So this, this tRNA will then be in the E-site. This tRNA will then be in the P-site, and then the A-site will be open for another amino acid carrying tRNA. So what this, what do the P and E sites stand for? Well you can see a little bit more clearly right over here. So the P-site is where you have the polypeptide chain actually forming, and, so the P-site is often, well, one way to remember it is is that's where you have the polypeptide chain, and now you have a new, you have a new A-site where you can bring in a new amino acid. And then the ribosome is going to shift, once this is bound, the ribosome, the peptide bond forms, and then the ribosome can shift to the right, when the ribosome shifts to the right, we're gonna be in this position, where the thing that was here, that was in the A-site, now the polypeptide is attached to it, it is now going to be in the P-site, and the thing that was in the P-site is now going to be in the E-site. It is now ready to exit, and that's why it's called the E-site. Because that's the site from which you exit. And so this is going to keep happening until we get to one of the stop codons. And when you get to one of the stop codons, then the appropriate polypeptide is going to be released, and we will have created this thing that could either be a protein, or part of a protein, so this is very exciting, because this is happening in your cells as we speak. This is, and in fact if you think about things like antibiotics, the way that they work are, is that, or the way that antibiotics work is that ribosomes and prokaryotes are different enough than ribosomes in plants and animals or in eukaryotes, that we can find molecules that hurt the function of ribosomes in prokaryotes, but don't do it to eukaryots. And so if you have bacteria in your blood stream, and if you take the appropriate antibiotic, it could disrupt this translation process in the bacteria, but not in your cells that you want to keep.