[Suspenseful music] [Felicia:] Psst! Psst! Cait. [Caitlin:] Nice get up. [Felicia:] I wrote you a note. [Caitlin:] A note? [Felicia:] That's right. A note. [Caitlin:] Okay. This isn't a note. This is gibberish. [Felicia:] It's not gibberish. It's a note, I just didn't want them to find out what I wrote you. [Caitlin:] Well, I can't read it. [Felicia:] Okay. Psst! Psst! Use this. [Caitlin:] Another note?! This is a cipher. [Felicia:] Exactly! [Caitlin:] So, I've got to use this to decode that. [Felicia:] That's right! [Caitlin:] All right. I'll play your game. Let's see... Okay. Q... Q is D... And then... That means A is N and N is A. The first part says DNA. Very clever. All right, that means the next... Q, D, E...Ah, I've got it! It says DNA Decoded. And this week, we'll find out how DNA gets its message across on... [Both:] DNA Decoded. [Music] [Felicia:] All right. It's time to get back to our cliffhanger. [Caitlin:] When we last met, RNA polymerase was hard at work, deep inside the nucleus of a cell, attached to the promoter region. RNA polymerase carefully added complimentary nucleotides to the template of DNA. All of a sudden, RNA polymerase stopped. She had just finished transcribing a gene into messenger RNA. All of a sudden, the newly-minted messenger RNA broke its bonds and exited the nucleus. Is that the end of our story? Is that the end of our hero? Or is it just the beginning of mRNA's quest? Dun, dun, dun. [Felicia:] You're such a nut. Hey, Cait. Let's actually show everyone the mRNA sequence that RNA polymerase made in the last video. Here it is. [Caitlin:] Remember, our DNA lives inside the nucleus. So, our RNA acts as a messenger, carrying the blueprints from the design office down to the factory floor where the proteins can be built. But, before we could build a protein, we need to translate the genetic instructions encoded in this mRNA molecule. [Felicia:] Can't we just use the translate app on our smartphones? [Caitlin:] I wish. Sadly, no. We're going to need some additional help from the cell. What the mRNA needs is a translator to decode the genetic instructions and a factory to build the protein. And fortunately, there is a molecule that does just that. It's called a ribosome. The ribosome splits into two pieces called subunits and when it encounters a strand of mRNA, the large and the small subunits bind themselves to the mRNA forming what I like to call a ribosome-mRNA sandwich. [Felicia:] Mmmm. A sandwich. [Caitlin:] Always thinking about food! The ribosome can read the code written in mRNA, format it, and use the code to assemble amino acids into proteins. The ribosome is like a magic decoder ring that reads the code written in the nucleobases of the mRNA and translates it into the corresponding amino acids. [Felicia:] Our genes encode for thousands of different proteins in our bodies using only four nucleobases. So, back to your question. How can four little letters create a code that would unpack so much complexity? [Caitlin:] Now, we're getting somewhere! So, what's the answer? [Felicia:] They use codons. Stick with me here... You might think the ribosome reads the nucleobases on the messenger RNA one at a time. If it did, there wouldn't be enough codes for all of the 20 amino acids that are used to build proteins. But that's NOT how the process works. Instead, the ribosome reads them in batches of three. [Caitlin:] Brilliant! [Felicia:] Each three letter code represents an amino acid to be added to the string of molecules that make up the polymer. [Caitlin:] Okay. So, now that we know the sequence of the amino acids required to build our protein, what comes next? How does the ribosome go about building a protein? [Felicia:] Exactly. Enter transfer RNA. Transfer RNA or tRNA is a piece of RNA that physically links the mRNA and the amino acids. tRNA is a bit like an adapter plug. On one end, it's bound to an amino acid. On the other end, it's bound to three nucleobases. This is the cool part. When transfer RNA finds mRNA with three nucleobases that correspond EXACTLY to its own nucleobases, the transfer RNA will bind to the mRNA. The three nucleobases on the mRNA are called a codon and the three nucleobases on the tRNA are called an anticodon, because they correspond to the codon precisely, according to Watson and Crick rules. Remember, the rules for RNA are A binds with U and C binds with G. [Felicia:] Okay, now. Let's look at an example. Take a minute to figure out the corresponding anticodons on tRNA. [Felicia:] So, here is what translation looks like when we put it all together. A newly minted strand of messenger RNA escapes the confines of a nucleus through a pore in the nuclear membrane, carrying a coded message to build a secret polymeric biomolecule, she ventures into the great beyond, racing against time to complete her mission. As fate would have it, she bumps into a ribosome. The ribosome enlists the help of his colleagues transfer RNAs who are able to translate her message. Three letters at a time, they decipher the coded message, codon by anticodon, until they've done it! They've built the top secret polymeric biomolecule! AKA, a protein. So, there you have it. Central dogma: DNA makes RNA and RNA makes protein. [Felicia:] So, we've cracked the genetic code from transcription to translation. [Caitlin:] Let's step back and look at the big picture. The sequence of nucleobases on a gene determines the sequence of nucleobases on messenger RNA. And the sequence of nucleobases on messenger RNA determines the sequence of amino acids in a protein. [Felicia:] The whole process outlined by Central dogma is pretty complicated. Isn't there a way to cut out the middlemen, like when you buy direct from the factory? [Caitlin:] You could... But the middlemen actually have their own purpose. Instead of just adding complexity, they add level upon level of control, like quality assurance. [Felicia:] I see... And here's another interesting twist for you. An amino acid can have more than one codon. In fact, almost ALL amino acids have more than one codon. It may seem a little counterintuitive but in fact this is a very good thing. It allows for redundancy in the genetic code, which provides a little wiggle room for transcription and for translation errors. Incredible! [Caitlin:] Absolutely. [Felicia:] After this video, you can try this out for yourself. We'll give you a series of codons and you can look them up in a table to figure out the corresponding amino acid. [Caitlin:] You'll get to test your skill as a DNA decoder.