In the time it takes you to watch this intro, your cells are going to do something amazing: They’re going to build billions of peptides — what are essentially baby proteins.

Unlike the chilli that I had for lunch, slowly working its way through my digestive system, this isn’t a process that you can feel. And on an unrelated note — Patti, boo, you got an antacid? …No?

Okay, all right… On the cellular level, proteins help build cells, kickstart chemical reactions, and support oxygen’s travel through the bloodstream, and much more. There are at least 10,000 unique proteins in your body alone. And to build these powerful molecules, cells take messages and turn them into a chain of parts that will eventually become proteins, like in a factory assembly line.

It’s a process called translation, and it’s happening in your cells right now! Hi, I’m Dr. Sammy, your friendly neighborhood entomologist, and this is Crash Course Biology.

Okay, so we’re gonna need to cut to theme music before my stomach decides to make its own. [THEME MUSIC] So far in this series, we’ve met our good friends DNA and mRNA. DNA is life’s big book of knowledge: It contains the information for how to make and run a living thing, in the form of molecules called nucleotides. They’re the basic building blocks of bigger information-carrying molecules called nucleic acids.

But DNA is locked away in the nucleus of a cell. That’s why we also have mRNA, a messenger, in fact, that’s what the M stands for. mRNA is a copy of a short section of DNA that can leave the nucleus, carrying along instructions for how to build a protein. Like DNA, mRNA also carries information using nucleotides.

And it works with four basic flavors of nucleotide, called Adenine, Uracil, Cytosine, and Guanine. A, U, C, and G for short. If this looks very similar to the nucleotides in DNA, that’s because they’re almost identical, with mRNA using Uracil as opposed to Thymine in DNA.

Proteins, meanwhile, are made of totally different molecules called amino acids. They’re speaking a whole different language than mRNA. So, how do we go from one to the other?

That’s where translation comes in. Now, mRNA translation isn’t exactly like going from English to Spanish. There’s no verb conjugation or oral exams that our genetic code has to worry about.

So, let’s get a better look at how it does work. mRNA’s nucleotide alphabet is always read in groups of threes. These three-letter “words” are called codons. And with a few exceptions, each one represents a possible amino acid.

So, the letters G-U-A represent valine. U-C-C is serine. And so on.

There are 64 possible combinations, which makes for a manageable genetic dictionary. By the way, those exceptions I mentioned, are called stop codons, they’re like periods telling us when a genetic sequence ends, and there are just three different codons that read as “stop”. The cellular machine responsible for translating these nucleotides into codons, and eventually connecting the amino acids, is called the ribosome.

It puts together amino acids to eventually build a peptide, kind of like how an assembly line turns a bunch of individual doo-dads into a brand-new electric car. Ribosomes themselves are made of protein and special RNA called ribosomal RNA. See how the ribosome is in two pieces?

That’s a feature, not a bug. When they aren’t actively translating, ribosomes spend a lot of their time separated like that. Translation occurs in three steps, and the first step, initiation, involves these two pieces working together.

First, the small half of a ribosome binds to the beginning of an mRNA strand. The start of practically every mRNA has the same three letters: A-U-G. It’s the start codon, and it codes for an amino acid called methionine.

A key ingredient that’s needed to start building a peptide. Except, the ribosome doesn’t just go off and fetch that methionine itself. Just like you wouldn’t leave your spot on the assembly line to go buy more supplies.

That would create a real backup of doo-dads at your spot. Enter transfer RNA, or tRNA. tRNAs are like the delivery truck of the translation world. There are dozens of types, and each is specialized to carry and install a specific kind of amino acid.

One end of a tRNA carries the amino acid itself, and the other has three unpaired nucleotides. tRNAs have what we call anticodons, which are complementary to codons. You can learn more about this in Episode 33, but to summarize: All nucleotides come in pairs — for instance, C always binds to G. So, the tRNA carrying methionine doesn’t have the A-U-G codon: Its nucleotides are U-A-C instead.

And when the tRNA rolls up to a ribosome, this allows it to attach to the mRNA. Those complementary nucleotides pair together, like the two ends of matching puzzle pieces. Once the tRNA arrives with methionine, it clicks into place on the mRNA, and that’s when the large half of the ribosome comes in and completes initiation.

Now that it’s switched on, the factory can really start assembling. The end of initiation means the amino acid chain has been started, and more links can be added to build a peptide. And that’s when elongation begins.

In this middle step, the ribosome scans the mRNA and reads its codons. As it does, more tRNA molecules drive up from the cytoplasm, the fluid inside a cell, and connect to the mRNA, carrying amino acids. The whole team is in sync, connecting different parts to build a whole.

Now, as far as factories go, ribosomes aren’t all that big. They can only hold three tRNAs at a time. So, a big part of the ribosome’s job is to string together those amino acid parts as quickly as possible, so that the tRNAs can get out of there and a new delivery truck can pull in with more parts.

The ribosome is done with elongation when it hits one of those three stop codons that I mentioned before, which signals to the assembly line that it’s time to wrap up translation. This last phase is called termination. Once the ribosome hits a stop codon, it releases its new amino acid chain and separates back into two pieces.

Then, the whole process can start again. That’s why the terminator says “I’ll be back.” That’s just the facts, man. Now, this amino acid chain isn’t a functional protein quite yet.

It’s an immature protein, called a peptide, which is made up of less than 50 amino acid links. These can combine with longer chains, or polypeptides. And eventually, peptides and polypeptides will fold up into functional shapes, sometimes coming together with others, to make — finally! — much larger, mature proteins.

So that’s how it works on the microscopic level. But big picture: proteins let us do just about everything that we do. Without them, we wouldn’t be able to play video games, kick a soccer ball, or make YouTube videos.

Proteins are really running the show, so the more we understand them, and the processes that create them, the more we understand how our own bodies function. We know that translation is happening in cells every second of every day, and get this: Virtually every living thing on Earth uses the same codons. Sometimes, scientists find tiny variations, but for the most part, the cells in everything from you to the bacteria on your kitchen sponge are speaking the same language.

You should probably get a new sponge, by the way, because unless its name is Bob and it has quadrilateral trousers, it shouldn’t be speaking. These similarities tell us that we’re all using a genetic code that’s been passed on from a single, common ancestor that lived billions of years ago! And billions of years later, cells have truly evolved into translation machines.

Like, consider this: scientists have spent decades learning how to build peptides in the lab, because they can be used in medications for things like diabetes, and chronic pain, and even cancer. But it’s slow going. Depending on the method, it could take scientists anywhere from about 40 seconds to an hour to add just one amino acid to a chain.

And the average protein is 300 amino acids long. On the other hand, animal cells like ours can add five amino acids to a peptide in just a single second. [mind blown] Evolution is such a show-off sometimes. Now, if you’ve watched the last couple episodes, you have officially seen all of the major steps in making a protein.

DNA is transcribed into mRNA, which is translated into chains of amino acids, which fold up into their final, protein forms like well-oiled genetic machines. But the story of how proteins get made definitely isn’t over! Now that scientists understand the basic pieces — which took decades, by the way — they’re finding new ways to /apply/ that knowledge.

Sometimes, that means building artificial proteins in the lab to use in medicine. And other times, that means sending instructions to ribosomes in our bodies telling those factories to get to work. I think it’s time for a visit to the Theater of Life… In 1985, biochemist Dr.

Katalin Karikó was sewing money into her daughter’s teddy bear. The research funding where Dr. Karikó worked in Hungary had just dried up, so she was immigrating to the United States to continue her work.

But this new chapter wasn’t going to be cheap. And her family was only allowed to bring so much money out of the country. What no one knew at the time was that the journey Dr.

Karikó was embarking on would save tens of millions of lives. See, Dr. Karikó’s work specialized in mRNA, and she believed these little genetic messengers could be used to tell cells how to make medicine for themselves.

But as she continued her work, she kept running into a problem: The mice that she tested on weren’t fans of lab-grown mRNA, and their bodies kept rejecting it. After years of work, Dr. Karikó and her colleague — an American named Dr.

Drew Weissman — finally found the missing ingredient. They learned that naturally occurring mRNA contains a molecule that lets it escape the immune system’s clutches. And when they added that to their artificial mRNA — boom!

The mice’s cells translated it, no problem. For 15 years, this discovery went largely unnoticed by the public. Not a lot of people were interested in mRNA.

But when, COVID-19 emerged, Karikó, Weissman, and other scientists used their experience with mRNA to develop the first vaccines for this disease. They created mRNA that tells cells how to make a protein that’s a part of the virus that causes COVID-19. Then, once our ribosomes help make those proteins, our immune systems can recognize them and learn how to fight them off.

So, if the real virus ever shows up, those cells are ready. From a distance, it can seem like the mRNA vaccines for COVID-19 — the ones distributed by Pfizer-BioNTech and Moderna — appeared out of nowhere. But the technology to make them had been tested, researched, and perfected for decades.

And now, all eyes are on mRNA, as scientists are considering what other diseases they could treat and prevent using this once-ignored technology. On most days, we only think about protein when we’re figuring out lunch or getting ready to hit the gym, but these molecules are so much more interesting and diverse than we tend to give them credit for. The blood in a fish, the chemical reactions in sunflowers, the mRNA vaccines keeping us safe — they all rely on proteins, and the ultra-fast ribosomes that make them.

And learning how protein creation works really makes us realize how efficient and powerful cells are — and just how much they can still teach us. In our next episode, we’re going to find out how our genes express themselves. I'll see you then!

Peace! This series was produced in collaboration with HHMI BioInteractive. If you’re an educator, visit BioInteractive.org/CrashCourse for classroom resources and professional development related to the topics covered in this course.

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