DNA, Hot Pockets, & The Longest Word Ever: Crash Course Biology #11

DNA, Hot Pockets, & The Longest Word Ever: Crash Course Biology #11

Ok, roll it. You know what this is? It is the longest word
in the world. Like, anywhere, in any language, ever. More than 189,000 letters. If you were to write it down, though I don’t
know why you would, it’d fill up more than 100 pages! And if you could actually say it without,
like, breaking your face, it’d take about FIVE hours! So what the frick is this word? It’s the name of the longest known protein
on earth. And it’s actually in you right now. Because of its enormous size, it was given
the nickname Titin by scientists. And that’s with two i’s. It’s a protein that helps give some of the
springiness to your muscles. Today we’re going to be talking about DNA
and how it, along with three versions of its cousin RNA, unleash chemical kung fu to synthesize proteins just like this. This is going to take a while to explain,
so how about if we make ourselves some hot pockets. Mmmm, my favorite. Ham and cheese. Every time I take a bite I wonder, how do
they do it? How do they pack exactly the same flavor into
every foil-cardboard wrapped foodish item? Clearly there has got to be some super secret
instruction manual kept in a location known to only two people. And since I’m talking about biology here,
that brings up a related question: How did I get built from the DNA instructions
and biological molecules we’ve been talking about? Today, that’s what I’m going to do. Not
actually make hot pockets, or a person. But I’m going to be talking about DNA transcription
and translation which is how we get made into the delicious
things we are today. Though hopefully none of us know how delicious
people are. Animals, plants, and hot pockets are really
nothing more than salty water, carbohydrates, fats, and protein, combined in precise proportions
following very explicit instructions. Let’s say I want to make my own hot pocket.
I would have to: 1) break into the lair of the Hot Pocket Company
holding the secret manual 2) read the instructions on how to make the
machinery to produce the hot pocket and the proportions of the ingredients 3) quickly write down that information in
shorthand before I get caught by the hot pocket police 4) go home and follow the instructions to
build the machinery and mix the ingredients until I have a perfect hot pocket.
That’s how we get us. Very simply, inside a cell’s nucleus, the
DNA instruction manual is copied gene by gene by transcription onto a kind of RNA then taken out of the lair where the instructions
are followed, by the process of translation to assemble amino acid strings into polypeptides
or proteins that make up all kinds of stuff from this titin down here to the keratin in
my hair. But most of the polypeptides that get made
aren’t structural proteins like hair, they’re enzymes which go on to act like the assembly machinery,
breaking down and building and combining carbohydrates and lipids and proteins that make up variations
of cell material. So enzymes are just like whatever ingenious
machinery ‘they’ use at the factory to make this. Let’s start in the lair — I mean the nucleus. The length of DNA that we’re going to transcribe
onto an RNA molecule is called our transcription unit. Let’s say, in today’s example, that it’s
going to include the gene that transcribes for our friend titin which, in humans at least,
occurs on Chromosome 2. Now each transcription unit has a sequence
just above it in the strand and that’s called “upstream” biologists call that “upstream” on the strand And that sequence defines where the transcription
unit is going to begin. This special sequence is the promoter, and
it almost always contains a sequence of two of the four nitrogenous bases we discussed
in our last episode: adenine (A), thymine (T) cytosine (C) and guanine (G). Specifically, the promoter is a really simple
repetition we’ve got thymine, adenine, thymine, adenine,
and then A-A-A. And on the other side: ATATTTT. Because you
know how this works, right!? This is called the TATA box. It’s nearly universal
and helps our enzyme figure out where to bind to the strand. Now, you’ll remember from our episode about
DNA structure that DNA strands run in one of two directions depending on which end of the strand is free
and which end has a phosphate bond. One direction is 5 prime-3 prime, and the
other is 3 prime-5 prime. In this case, upstream means toward the 3
prime end and downstream means toward 5 prime. So the first enzyme in this process is RNA
polymerase, and it copies the DNA sequence downstream of the TATA box that’s towards the 5′ end and copies it into a
similar type of language: messenger RNA [mRNA]. Quick aside: So you’ll notice that to read
the DNA in order to make enzymes we need an enzyme in the first place. So it kind of gets “chicken vs egg” here. We need the enzyme to make the DNA and the
DNA to make the enzyme. So, where did RNA polymerase come from if
we haven’t made it yet!? What an excellent question! It turns out all of these
basic necessities get handed down from your Mom. She packed quite a bit more into her egg cell
than just her DNA so we had a healthy start. So, thanks Mom! So the RNA polymerase binds to the DNA at
that TATA box, and begins to unzip the double-helix. Working along the DNA chain, the enzyme reads
the nitrogenous bases, those are the letters and helps the RNA version of the nitrogenous
bases floating around in the nucleus find their match. Now as you ALSO might recall from our previous
episode nitrogenous bases only have one counterpart
that they can bond with. But RNA, which is the pink one here, doesn’t
have thymine like DNA does which is the green and the blue. Instead it has uracil (U), so U appears here
in T’s place as the partner to adenine. As it moves, the RNA polymerase re-zips the
DNA behind it and lets our new strand of messenger RNA peel away. Eventually, the RNA polymerase reaches another
sequence downstream, called a termination signal, that triggers it to pull off. Now, some finishing touches before this info
can safely leave the lair. First, a special type of guanine (G) is added
to the 5-prime end that’s the first part of the mRNA we copied and this is called the 5′ cap. On the other end, it looks like I fell asleep
with my finger on the A key of my keyboard but another enzyme added about 250 adenines
on the 3′ end. This is called the poly-A tail. These caps on either end of the RNA package
make it easier for the mRNA to leave the nucleus and they also help protect it from degradation
from passing enzymes, while making it easier to connect with other organelles later on. But that’s still not the end of it. As if
to try to confuse me to protect the secret hotpocket recipe the original recipe book also contains lots
of extra, misleading information. So just before leaving the nucleus, that extra
information gets cut out of the RNA in a process called RNA splicing. And it’s. something. like. editing. this.
video. The process is really complicated, but I just
had to tell you about two of the key players because they have such cool names. One, the Snurps, which are Small Nuclear RibonucleoProteins. These are a combination of RNA and proteins,
and they recognize the sequences that signal the start and end of the areas to be spliced. Snurps bunch together with a bunch of other
proteins to form the spliceosome, which is what does the actual editing as it were, breaking the junk segments down
so their nitrogenous bases can be reused in DNA or RNA, and sticking together the two
ends of the good stuff. The good stuff that gets spliced together,
by the way, are called exons because they’ll eventually be expressed the junk that gets cut out are just intervening
segments, or introns. The material in the introns will stay in the
nucleus and get recycled. So for instance, titin down there is thought
to have hundreds of exons when it’s all said and done probably more than 360, which may be more
than any other protein. And it also contains the longest intron in
humans, some 17,000 base pairs long. Man, titian! It is just a world record holder! So now that it has been protected and refined,
the messenger RNA can now move out of the nucleus. OK, a quick review of our Hot Pocket Mission
Impossible caper so far: We broke into the lair containing the instructions,
we copied down those instructions in shorthand we added some protective coatings, and then
we cut out some extra notes that we didn’t need and then we escaped back out of the lair. Now I have to actually read the notes, make
the machinery and assemble the ingredients. This process is called translation. So next, rewind your memory — or just watch
that video again — to the episode about animal cells. Do you remember the rough endoplasmic reticulum? I hope you do. Those little dots on the membranes are the
ribosomes, and the processed messenger RNA gets fed into a ribosome like a dollar bill
into a vending machine. Ribosomes are a mixture of protein and a second
kind of RNA, called ribosomal RNA [rRNA] and they act together as a sort of work space. rRNA doesn’t contribute any genetic information
to the process, instead it has binding sites that allow the incoming mRNA to interact with
another special type of RNA the third in this caper, called transfer RNA,
or tRNA. And tRNA really might as well be called ‘translation
RNA’ because that’s what it does it translates from the language of nucleotides
into the language of amino acids and proteins. On one end of the tRNA is an amino acid. On
the other end is a specific sequence of three nitrogenous bases. These two ends are kind of matched to each
other. Each of the 20 amino acids that we have in
our body has its own sequence at the end. So if the tRNA has the amino acid methionine
on one end, for instance, it can have UAC, as the nucleotide sequence on the other. Now it’s like building a puzzle. The mRNA
slides through the ribosome. The ribosome reads the mRNA three letters
at a time – each set called a triplet codon. The ribosome then finds the matching piece
of the puzzle: a tRNA with three bases that will pair with the codon sequence. That end of the tRNA, by the way, is called
the anticodon. Sorry for all the terminology. YOU NEED TO KNOW IT! And of course, by bringing in the matching
tRNA, the ribsome is also bringing in whatever amino acid is on that tRNA. Ok so, starting at the 5′ end of the mRNA
that’s fed into the ribosome, after the 5′ cap, for almost every gene, you find
the nucleotide sequence AUG on the mRNA. The ribosome finds a tRNA with the anticodon
UAC, and on the other end of that tRNA is methionine. The mRNA, like a mile-long dollar bill, keeps
sliding into the ribosome so that the next codon can be read, and another tRNA molecule
with the right anticodon binds on. If the codon is UUA, the matching tRNA has
AAU on one end and Leucine on the other and if the mRNA has AGA, the matching tRNA
has UCU on one end and Arginine on the other. In each case that new amino acid gets connected to
the previous amino acid – starting a polypeptide chain. Which is the beginning, the very beginning
of a protein. But it turns out there are LOTS of different
ways to read this code. ‘Cause UUA is not the only triplet that
codes for Leucine — UUG does too! And argenine is coded for by six different
triplets! This is actually a good thing. It means that
we can make a few errors in copying, transcribing and translating DNA, and we won’t necessarily
change the end product. This process continues, with the mRNA sliding
in a bit, the ribosome bringing in a tRNA with an amino acid, that amino acid binding
to the existing chain and on and on, sometimes for thousands of
amino acids to make a single polypeptide chain, for example. This whole word is basically just the names
of the amino acids in the sequence in the order in which they occur in the protein all 34,350 of them. But before we can make our own hot pockets and that string of amino acids becomes my
muscle tissue we have some folding to do. That’s because proteins, in addition to
being hella big, can also contort into very complex and downright lovely formations. One key to understanding how a protein works
is to understand how it folds, and scientists have been working for decades on computer
programs to try to figure out protein folding. Now, the actual sequence of amino acids in
a polypeptide – what you see scrolling along down there – is called its primary structure. One amino acid covalently bonded to another,
and that one to another, in a single file. But some amino acids don’t like to just
hold hands with two others, they’re a bit more promiscuous than that. The hydrogens on the main backbone of the
amino acids like to sometimes form bonds on the side (hydrogen bonds) to the oxygens on
amino acids a few doors down. When they do that, depending on the primary
structure, they bend and fold and twist into a chain of spirals, called a helix. We also find several kinked strands laying
parallel to one another, called pleated sheets. All those hydrogen bonds in pleated sheets
are what make silk strong, for instance. So in the end, our promiscuous amino acids
lead to wrinkled sheets. Ah-hah! These hydrogen bonds help give polypeptides
their secondary structure. But it doesn’t end there. Remember the R groups
that define each amino acid? Some of them are hydrophobic. Since the protein
is in the cell, which is mostly water, all those hydrophobic groups try to hide from
the water by huddling together, and that can bend up the chain some more. Other R groups are hydrophilic, which if nothing
else means that they like to form hydrogen bonds with other hydrophilic R groups. So we get more bonding, and more bending,
and our single-file line has now taken on a massively complex 3-D shape. It also explains why I can fix my bed-head
by wetting my hair with water. The water helps break some of those hydrogen
bonds in the keratin which relaxes its structure. That way I can comb it out, and when it dries
those bonds reform and voila, perfect hair. All of this shape caused by bonding between
R groups gives our polypeptide a tertiary structure. So now we have a massively contorted polypeptide chain, and it actually contorts very precisely. Sometimes, just one chain is what makes up the whole enzyme or protein. In other proteins, like hemoglobin, several
different chains come together to from a quaternary structure. So a quick review of structure: the sequence
is primary, the backbone hydrogen bonds forming sheets and spirals are secondary, R group
bonds are tertiary, and the arrangement of multiple proteins together give quaternary
structure. These polypeptides are either structural proteins,
like this thing at the bottom here that you can find in muscle or in my hot pocket. They might also be enzymes, and enzymes like,
do stuff. They can cut up biological molecules like
I do with this chef’s knife, they can mix stuff and they can put stuff together. So from that one recipe book we got all of
the ingredients and all of the tools necessary to make me, which is better than a hot pocket. Would you all agree? Now take your time with this stuff, feel free
to watch the episode a couple of times, because next week we’re going to talk about how
cells swap all of this genetic information through reproduction. Thank you for watching this episode. By now, you should probably know how this
works. You can click on any of the links over there,
and it’ll take you back to that point in the show as long as you are not watching on your
cell phone. It doesn’t work on cell phones, I apologize
for that. Thank you to everyone who helped us put this
show together, and thank you to you, for watching it today. If you have any questions about this episode
please leave them in the comments below, or you can get us on Facebook or Twitter. And that’s all. Goodbye!

100 Replies to “DNA, Hot Pockets, & The Longest Word Ever: Crash Course Biology #11”

  1. If anybody wants a simple way to figure out the difference between transcription and translation, this helps me:
    DNA and RNA share the same language of nucleotides. They can write to each other, and just TRANSCRIBE information between them.
    DNA and proteins, however, don't share a language. DNA 'speaks' in nucleotides, and proteins 'speak' in amino acids. So they need RNA to TRANSLATE the information shared between DNA and the proteins.

  2. Why does it have such a long name? I am truly disturbed by this. I can not stop thinking about why, how, and when this name was created. I hate it.

  3. Also, if you watch at .75 speed, it sounds more understandable and at a normal pace. At .5 speed, he sounds drunk but still smarter than any one I personally know LOL.

  4. "sorry for all the terminology"
    NO! For gods sake man, I have a midterm in two days. More terminology. Save us Obi-Hank, you're our only hope

  5. At exactly 2:16 there's a break in the letters therefore it's no longer a single word

  6. Crash course helped me pass my psychology class in college, now I'm back for biology, so thank you for all that you do.

  7. "What are you going to name the Splice thing, professor?"

    "The… Ummm…. Uhhhh…. Splice… osome? Spliceosome???? I guess???"

  8. Hank being better than a hot pocket is a pretty low bar. You are way better than a hot pocket you've never given me 3rd-degree burns on the roof of my mouth and you've never given my suicidal ideations.

  9. I think I misunderstood part of this video. When he said that introns are removed from the sequence before the mRNA is made so these parts are not turned into proteins, but then he said that titin had tons of introns in it? Did I miss something? Maybe he said exons, there was a lot going on. Anyway, great video! I have heard that they discovered in lab mice that if intron sequences are removed, that many of the mice either die or have serious health issues, any thoughts on why? Anyway, great video as always

  10. 7 years later and this still helps me with school … amazing! Your videos truly transcend time!
    Keep up the great work!

    Yes, Hank, I think we'd all agree that you are better than a hot pocket

  11. can u also make a video on nomenclature, physical and genetic continuity of extrachromosomal inheritance and the maternal inheritance..i just get confused on other videos..please please…thank you

  12. I can make the longest word and it will take a second to read because all of it will be silent

  13. I've been searching for videos on this very topic for some time now, since it's such an amazingly complex and fascinating issue, regarding the intrinsic relation between raw data and the information it contains.
    Also, Hank probably is my favorite YT-er and always imagined he would have already done some high-quality video on this. So, I'm glad to have found it and impressed by the detail and simplicity there's in this video, taking into account the nature of the topic.

    However, I didn't expected all those weird faces, the sensual poises, and the sexual references coming thru the whole video. Which weren't easily ignored when playing the video at 0.75 of its velocity rate.
    Never my learning techniques backfired to me as much as in this case..

  14. I swear to god you're better than my teacher I LOVE THOSE VIDEOS MY LIFE AND SCHOOL LIFE MAKES MORE SENSE NOW

  15. The reason the name is so long is because it has all of Titian’s amino acids in it. That’s up to 33000 amino acids.

  16. Titin= Methionylthreonylthreonylglutaminyrginyltyrosylglutaminlserylleucylphenylalnylvalylthreonylleucylgl Ycylaspartylprolylglycylisoleucylglutamylglutaminylserylleudyllysylisoleuylaspartylthreonylleucylisoleu… I'm so lost!!!

  17. At 4:11 I'm confused by the 5'==>3' (upstream) image. It looks as if the arrow is pointing in the direction of 3' ==> 5'

  18. Methionylalanylthreonylserylarginylglycylalanylserylarginyl be like: long live the king
    (shoves supercalifragilisticexpialidocious off the cliff into the stampede)
    Pseudopseudohypoparathyroidism: NOOOOOOOOOOOOOOOOOOOO

  19. I swear to god these crash course videos are more valuable than both my high school and college educations combined

  20. where shold i go not to see you on YouTube you😄 in history ethics biology you are everywhere you genius 😁I like to you explains in detail thankyou 😚

  21. Nice, but all I could think of during the entire video is the fact that hot pockets are made out of chopped up pig carcasses and chicken periods.

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