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The Nucleus
Written by Tim Sheppard MBBS BSc. Last updated 9/11/10

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What is the nucleus?

It is arguably the most important object in a cell; the nucleus contains all of the genetic material, and without it, a cell will have no idea how to manufacture its proteins. It's true that some cells cope with out - red blood cells are an obvious example. However, the nucleus - often referred to as the 'brain' of the cell - contains the DNA of the cell, and with DNA's essential function, it's not something which can be ignored.

Of course, associated with every complicated function is a complicated structure. In the grand scheme of things, the nucleus could be considerably more complicated, but it is still quite a difficult structure, with certain key parts to understand, which is what the rest of this page will concern itself with. The important thing to remember, most simply, is that the nucleus is where the DNA is stored, and it is sometimes known as the 'brain' of the cell.

A little more detail helps us to understand how exactly the nucleus works, but unfortunately it turns what is essentially a simple explanation (the brain of the cell) into a far more complicated affair. As with all structures, each part has been cleverly designed to cope with the demands placed upon it, making every intricate detail very important.

The animation on the left shows how each part of the nucleus is labelled. Importantly, it is only the black and grey parts in the centre that are, strictly speaking, concents of the nucleus. The nucleus is surrounded by a membrane (like many organelles) but unlike many organelles, the nucleus's membrane is doubled back to form an envelope - the nuclear envelope. This means that the surrounding of the nucleus has two layers, or a bilayer, with a space in between known as the perinuclear space. This space is continuous with something known as the rough endoplasmic reticulum - that is, the nuclear envelope opens out into the endoplasmic reticulum (ER), so the contents of the perinuclear space can mix in with the contents of the ER.

Inside the nucleus there is something known as the nucleolus. This is where ribosomal RNA is produced. Surrounding the nucleolus is something known as the nucleoplasm, which is made up of heterochromatin and euchromatin. These are both forms of DNA which have been condensed so that they take up less space, and it is here that mRNA and tRNA are produced.

Finally it is important to consider the nuclear pore, without which the nucleus would be useless. Essentially the nucleus doesn't operate independently of the cell - the reactions which take place in the nucleus produce important molecules which have to leave and perform their job elsewhere in the cell. To do this, they need an escape route, and that is the role of the nuclear pore.

What are heterochromatin and euchromatin?

As previously mentioned, these are forms of genetic material or DNA which have been condensed to take up less space. They have been wrapped around proteins so that they are coiled up, and can fit into a relatively tiny nucleus - after all, the amount DNA in a normal human cell could stretch to almost 2 metres. However, they haven't quite been wrapped in the same way, hence the different names, and their different purpose explains why they are wrapped differently.

Hetero- means 'other' or 'different', and chromatin is just the name given to genetic material when it's wrapped around proteins. It's not difficult to see, then, how heterochromatin means the genetic material which belongs to other cells. Every cell in the human body contains all the genes required by any cell - that is, even the skin cells in your foot have the same genes in them as the cells of your brain. The difference is that some genes are used, and some are not - those cells important for skin's function will be used in skin cells, but not necessarily in brain cells. Any genetic material which isn't needed is wrapped up in a certain way, and stored as heterochromatin.

Eu- can either mean 'true', or it can mean 'the product of a particular substance'. In the context of genetic material, it means the genetic material which is true to that cell - the product of the genetic material which is relevant for this cell. It's almost like the opposite of heterochromatin, because euchromatin is made up of the genetic material which is required by that cell.

To get the DNA into such a small space, it is wound around special proteins called histone proteins. There are five important histone proteins which are of particular interest to us at the moment, known as H1, H2A, H2B, H3 and H4. The latter four come together as a group of four which is known as a nucleosome. Each nucleosome is able to wrap 146 base pairs around it; that is, you can get 146 nucleotides on each DNA chain in the double helix around each nucleosome.

To get lots of DNA wound up, you just need to put lots of nucleosomes together then, right? Well, almost. You could shorten your DNA molecule a lot by doing this, but you really need it considerably shorter, so you wind it up another way. There are 50 base pairs between each nucleosome, which could potentially increase the length of the chromatin a lot. However, these are wrapped around the fifth histone protein (H1), which coils the chain up further.

Just for good measure, this chain of nucleosomes is further wrapped around even more proteins. This creates something which is super-coiled, and very, very condensed, known as euchromatin. It's very wound up, but it can still be accessed when it needs to be transcribed or replicated.

Heterochromatin, however, doesn't really need to be accessed at all - it's the genetic material which isn't needed for this cell. So we might as well wrap this up even more - it needs to be there, but we can condense it as much as possible. This is exactly what happens. The reason it will always be shown as a darker colour than the euchromatin in images is that it is so condense. When you are trying to produce an image of something very small, you use something called electron microscopy, which produces an image that depends on how condense the electrons are. (Note that the nucleus referred to in relation to atoms, around which electrons orbit, is different from the nucleus of a cell, referred to on this page). Something which is more condensed will bring electrons closer together, hense heterochromatin appears darker.

What is a nuclear pore?

I spoke earlier about how important the nuclear pore is - and this is true. It has an essential function to carry out - import and export. Everything that is needed to manufacture DNA and RNA has to get into the nucleus, and each required thing enters through one of around 4000 nuclear pores. Similarly, every molecular of RNA produced to manufature proteins has to get out, and does so through one of the many proteins.

The nuclear pore is a kind of hole in the side of the nucleus which allows entrance of chemicals required in DNA and RNA manufacture (molecules such as ATP and the proteins required to make ribosome subunits), and the exit of RNA molecules and ribosomes subunits from the nucleus. Although we know a lot about what it needs to do, and what it does, we don't know a lot about how it does it! The nucleus is small enough as it is - if you get a light microscope (the kind found in science class at school), you can barely see the nucleus, and even a powerful light microscope will not make out the difference between heterochromatin and euchromatin. To see what's going on at a nuclear pore, then, is incredibly difficult, so what we do know is quite impressive!

From what we can make out, a nuclear pore is made up of about 100 subunits of proteins. This includes eight on the nucleoplasm side, and eight on the cytoplasm side, known as the inner and outer rings respectively. These are basically subunits of proteins which are on the inside and outside of the nuclear envelope. Protruding towards the centre of the pore from each of these subunits is something called a spoke, which is a mixture of yet more protein subunits. In the centre of these spokes is a plug, seen in orange in the images in this section. The spokes and plug mean that a pore, which can be over 100nm in diameter, will not let anything through if it is greater than 9nm. Another measure is weight - that is, anything heavier than around 60,000 Daltons will not get through easily.

That may sound very heavy, but 60,000 Daltons is not actually that much; most proteins and RNA molecules will weigh a lot more than that! So how do the RNA molecules get out? Well, anything that weighs less than 60,000 will happily get through through simple, passive diffusion. Anything above that weight (or bigger than 9nm) needs to have some help getting across. So, if a protein wants to get into the nucleus, it needs to have a nuclear import signal or nuclear localisation sequence.

When proteins are produced in the cell, they will all have a specific target - some go to the nucleus, some go to the endoplasmic reticulum, some want to leave the cell entirely etc. If something needs to go to the nucleus, it will be synthesised with a special sequence: this nuclear localisation sequence, which is something recognised by molecules on on the outside of the nuclear pore. These molecules bind to the protein entering the nucleus, and guide it through, using energy from the hydrolysis of ATP to get it through the small gap.

It may seem quite complicated, but the amount we understand is really quite limited. For example, we don't quite know how things get out of the nucleus - though we think the molecules which guide things into it can also guide things out. Still, we know what needs to go on at a nuclear pore, and we know that they're a very important part of the nucleus.

Further Reading