tMoL: Nucleus

The brain of the cell. It is one of the most well known elements of an animal cell, and is common to all higher organisms (eukaryotes – animals, plants,fungi), as with most structures inside a cell it does not occur in bacteria (prokaryotes). Most DNA in a cell is found in the nucleus, it is the storage centre for all of the information to make more cells. The nucleus is also full of proteins which control which genes are active in a cell and help to pack all of the DNA into such a tiny space. This is how cells are able to become specialised to a specific function, by controlling which genes are active.



The nucleus is essentially a hollow sphere, the outside consists of two membrane layers (nuclear envelope), similar to the cell membrane, made up of layers of fats (lipids). This allows the inside of the nucleus to be very different to the outside, allowing more complicated and accurate control of gene activity and protecting you DNA from being damaged. There is a region within the nucleus called the nucleolus, which contains specific parts of your DNA, involved in making rRNA (needed in large amounts as part of the protein manufacturing machinery). The rest of the nucleus was, until recently, though to be very variable, but it now appears that certain regions are reserved for certain functions.

It seems that pieces of DNA which are not very active i.e. that carry silent genes, are often found near the outer edge of the nucleus, whilst more active genes are closer to the centre. The reasons for this are currently unclear and highly argued over. It may be that genes move to the centre because they are active, alternatively genes may be moved to the centre in order to become active. Active and silent genes are often linked together on the same piece of DNA which loops between the periphery and the centre of the nucleus. Some recent studies have also shown that, in some cell types, the same genes on different pieces of DNA are usually close together which may mean that they are controlled similarly. Sequences on one piece of DNA can also affect the activity of genes on others.

There are over 2 metres of DNA in each one of your cells, in order to fit all of this into the nucleus a group of proteins called histones help to tightly coil the DNA. Eight histones (two each of histones 2A, 2B, 3 and 4) work together to wrap DNA around themselves. Active genes are only loosely wrapped, whilst silent genes are more tightly wrapped and use extra proteins (including Histone1) to pack the DNA together more tightly. The tightest coiling occurs when a cell is dividing to make more cells, this is when each chromosome (DNA chain) adopts the classic X shape.

Access to the nucleus from the rest of the cell is via nuclear pore complexes, a large organised structure composed of many different proteins all working together. Anything that needs to move between the nucleus and the rest of the cells must bind to importins or exportins; proteins which allow transport through the nuclear pore complexes. Nuclear export requires energy to move proteins across the nuclear envelope.

RNA is made in the nucleus, using DNA as a template, but is functional in the cytoplasm so must be exported from the nucleus through the nuclear pore. mRNA carries the information from a gene which is used to make a protein, whilst tRNAs and rRNAs are needed to build the machinery which makes proteins using mRNA as a guide. All proteins are made outside the nucleus, but many have functions inside the nucleus and so much be imported. Controlling import of proteins which regulate gene activity is a common way of regulating which genes are active and when.

Proteins within the nucleus include histones, mentioned above, as well as polymerases and gene regulators. Polymerases are made up of several proteins and are responsible for using the information coded in DNA to make more DNA (allowing cells to divide and make new cells) and also to make RNA, needed to make new proteins. Particularly in more complex organisms there are then hundreds of gene regulators. These are proteins which bind to specific regions of DNA (sequences) and affect the likelihood of polymerases targeting nearby genes. An activator protein will aid polymerase binding and so increase the amount of mRNA (and hence protein) from nearby genes, whilst a silencer will reduce the amount of protein production. Many of these interact to fine tune the activity of any one specific gene. Some can even act over very long distances or between chromosomes, which is thought to be dependent upon the careful arrangement of genes within the nucleus.

The major advantage of having a nucleus, which can be seem in the differences between bacteria and higher organisms, is that the DNA is better protected, and so the genome can become much larger and alternative splicing becomes possible. This is where an mRNA from a specific gene can be edited (have bits removed) to give the resulting protein different functions. Only once the mRNA is edited can it be exported from the nucleus and made into a protein. This allows one gene to make many different proteins, so we can become more complex without drastically increasing the number of genes we have. The prime example of this is a gene in fruit flies (Drosophila melanogaster) called Dscam which can produce upto 38016 different proteins from just one gene.

Most cells have one nucleus although there are several exceptions. The most common is mammalian red blood cells, during maturation these cells lose their nucleus allowing them to store oxygen more efficiently and to move more easily through smaller blood vessels. These cells have a limited lifespan as they stop making new proteins soon after losing the nucleus and so can only survive a few days before their structures begin to decay. Other cells have more than one nucleus. Many liver cells usually have two, this makes them better able to survive all of the toxins that the liver processes everyday. Cells in muscles fuse together leading to single large cells with many nuclei called syncytia. This also occurs in the placenta during mammalian development. The nucleus in the early drosophila embryo goes through several cycles of division before the cell itself starts to divide, this produces a syncytium with hundreds of nuclei in one cell.

The nucleus is the control centre of the cell, it is responsible for coordinating all of the decisions in the life of the cell, controlling when to divide and what to become. Many complex mechanisms are involved in this regulation and are aided by the separation of the nuclear environment from the rest of the cell. The existence of the nucleus is what has allowed us to develop from bacteria and to establish such complex body shapes and structures.