Science Lesson: DNA (Part7, The Ribosome: Cellular Machine and Remnant From an RNA World)


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The Ribosome (A Brief Intro)

As many of you are already aware, and as we previously discussed the ribosome is a component of the cell (it's labeled on the figure above, there are many of them that sit on the surface of the cellular organelle called the rough endoplasmic reticulum), where an messenger RNA (mRNA) is used to produce a protein. It is here that specialized RNA molecules called tRNA or transfer RNA read each mRNA template and bring together the correct amino acids to construct a protein based upon the sequence that the mRNA codes for. As we also previously discussed the ribosome is comprised of several parts, some of which are RNA and others are protein. Today we will discuss the ribosome a bit further, we will take a look at one and take it apart into it's individual pieces so that you can see what it looks like. We will also discuss a fun hypothesis called the RNA world hypothesis. Lots to talk about, so let’s get started!

Enzymes

An Enzyme is defined as a biological catalyst that allows for a chemical reaction to occur quickly in a controlled environment. Most everyone thinks of enzymes as proteins, but this is not always the case! There are also nucleic acid enzymes made out of RNA called Ribozymes. Ribozymes are sequences of RNA that can fold into specific shapes which allow them to do the same things that protein enzymes do! They orient molecules in the proper ways to force them to quickly and easily react! Prior to 1967 everyone thought that all enzymes were proteins however some scientists (Carl Woese, Francis Crick (who you may know as the guy who along with James Watson determined that DNA was a double helix) and Leslie Orgel proposed that because RNA could fold into particular structures (due to its single stranded nature it can interact with itself in unique ways) that it might be possible for RNA to also catalyze reactions. A few years (scientifically speaking) in 1980 a different scientist named Tom Cech found one such Ribozyme and subsequently won a Nobel Prize for it. The point of all of this is proteins are not the only structure in the cell capable of doing chemistry, and unbeknownst to many since its discovery in the 1950’s; the Ribosome is another one of these catalytic RNA structures! It wasn’t until the early 2000’s when X-Ray crystallography technology allowed us to actually see the structures of the Ribosome that this all became clear.

The Structure of the Ribosome

So why don’t we take a look at what this important, protein making cellular machine is! For simplicities sake we will take a look at the bacterial ribosome rather than the eukaryotic one, know that they are similar however the bacterial complex is slightly smaller with fewer components (although there are still a ton of them). Everything ends up being bigger and much more complex (yet performs the same function) when you deal with eukaryotic proteins and enzymes. The bacterial ribosome (I will use the structures from the bacterium Thermus thermohphilus PDB File 4V5M) is divided up into two pieces called the 30S subunit, and the 50S subunit. Let’s take a look at each of these individually:

30S Ribosome Subunit (Thermus thermophilus)

The first of two major subunits of the ribosome is comprised of an RNA strand called the 16S RNA which is complexed with (interacts with) 21 different proteins. This 30S subunit is where the mRNA template binds and moves such that the sequence can be read and the protein assembled (assembly happens in the other subunit the 50S) (Citation):

Figure 1: The 16S RNA


Source: Self with use of protein database file 4V5M

Here you can see the RNA component of the 30S Subunit, it doesn’t look like any nucleic acid structure you’ve seen before right? RNA is single stranded and so it doesn’t form into that rigid double helix that DNA does. It’s able to fold back on itself and interact in unique ways, when the strands get long (this one is over 1500 bases) they can end up looking like this, a jumbled mess (to use the scientific term :) ). However it is these unique folds that lead to small pockets inside that allow chemistry to happen! This RNA does not fold into this odd shape all on its own, it also has 21 different proteins bound to it:

Figure 2: The 16S RNA (Black) With Bound Proteins (Colors)


Source: Self with use of protein database file 4V5M

Here I have colored the nucleic acid material black so you can better visualize the proteins bound to it (which I have given colors). I have taken the structure and rotated it 360° on the horizontal axis so you can see that the proteins cover all of the surfaces of the RNA. They are there for structural purposes, and aide in this large RNA strand keeping that unique (messy looking) fold that it has.

50S Ribosome Subunit (Thermus thermophilus)

The second subunit of the bacterial ribosome is the 50S, which is comprised of two nucleic acid molecules (23S RNA and 5S RNA) as well as 31 different proteins. This is the piece of the ribosome that is responsible for catalyzing the formation of the bonds between the amino acids in a growing protein (peptide) chain. (Citation) Let’s begin by looking at the two RNA chains:

Figure 3: 23S RNA and 5S RNA

23S RNA

5S RNA


Source: Self with use of protein database file 4V5M

23S and 5S Together


Source: Self with use of protein database file 4V5M

Here you can see that the 23S is an even larger structure than the 16S (it is made up of a staggering ~2900 RNA nucleotides), while the 5S is comparatively a tini structure (only 122 nucleotides). Attached to these two RNA molecules are a collection of 31 proteins (27 of which are seen in the structure file I have):

Figure 4: The 23S RNA, 5S RNA and All Bound Proteins


Source: Self with use of protein database file 4V5M

Here like for the 30S subunit I have colored the nucleic acid material black so you can better visualize the proteins bound to it (which I have given colors). I have taken the structure and rotated it 360° on the vertical axis so you can see that the proteins cover all of the surfaces of the RNA.

Figure 5: The Complete Ribosome

Full Assembly of the Nucleic Acids


Source: Self with use of protein database file 4V5M

Here I have displayed for you the three nucleic acid components only, with the colors that I previously assigned them when we discussed each of them. So you can see how the 16S (blue) 23S (Red) and 5S (orange) RNA’s all stack and interact with one another.

Complete Nucleic Acid Structure With Proteins


Source: Self with use of protein database file 4V5M

And here is the grand reveal, the complete (well… almost) bacterial ribosome. The protein factory for the bacterial cell, which is functionally conserved in all higher species (like you!) as well! It’s big and it’s messy looking, but they are responsible for generating all of the proteins that every single one of your cells, and all living cells on the planet need for their survival.

RNA World Hypothesis

The final topic I would like to discuss with you all is the RNA world hypothesis, this is an idea that all life on earth began as self-replicating RNA. This hypothesis was another proposal of the previously mentioned Carl Woese, and he thought that since it is possible for RNA to do all of the functions necessary for its own replication by itself: it can store information (like DNA was later evolved to do) and can catalyze reactions (like proteins were later evolved to do), that life began with “organisms” that were purely just RNA molecules. However as the molecules became more complex, additional mechanisms were evolved to accomplish these tasks. The ribosome seems to fit this hypothesis, as it is really just an RNA machine. Yes there are proteins involved, but they don’t seem to be doing any of the chemistry, that is left to the RNA. What do you think? Is Woese right and it’s indeed possible that life began with self-replicating RNA and the ribosome is has been carried over from this early time?

I hope that this blog has given you a greater appreciation for the magnitude of the complexity of the chemistry happening inside of us. The ribosome is just one of many components of the cell, and as you can see it takes a huge number of different proteins (most of which we don’t understand at all!) and three huge RNA molecules with incredibly complex folding patterns, to allow proteins to be synthesized. Life is unbelievably complex and yet so very simple and logical (most of the time) all at once! It’s amazing to see, and fascinating to learn about!



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