The nucleolus (plural: nucleoli) is a well-studied compartment of the nucleus. This is where most of the cell’s ribosomal RNAs (rRNAs) are transcribed and then combined with proteins to form the subunits of the ribosome. The suborganelle was originally discovered in eels by the Italian scientist Felice Fontana in 1774. He was able to see the large, darkly stained nucleolus under a simple light microscope. However, its function wasn't discovered until two centuries later.
The nucleolus is not enclosed by a membrane like other organelles, but instead is made up of interconnected ribosome precursors and loops of DNA. These loops contain clusters of rRNA genes and are referred to as nucleolar organizer regions, or NORs. Three of the four rRNA transcripts, 5.8 S, 18 S, and 28 S, are made here. The fourth, 5S, is made in the nucleus and brought into the nucleolus to be assembled with the other three into ribosome subunits. Nucleoli can be divided into three regions: a fibrillar center (FC), a dense fibrillar component (DFC), and a granular center (GC). All three regions can be seen with an electron microscope. The fibrillar center is a globular region that contains hundreds of rRNA genes that are not currently being transcribed. The dense fibrillar center contains rRNA genes that are actively transcribed by RNA polymerase I. The granular center is where the rRNAs are processed and proteins are added to the rRNA to form ribosomal subunits. Once finished, these subunits pass through the nucleus into the cytoplasm where they synthesize proteins in a process called translation.
The nucleolus has an extremely high concentration of proteins, often the highest anywhere in the cell. Proteins that are destined for the nucleolus contain a special sequence called a Nucleolar Localization Signal, which targets the proteins to the nucleolus. This sequence is similar to the Nuclear Localization Signal which targets proteins to the nucleus. Major proteins present in the nucleolus include nucleolin, fibrillarin, spectrin, and B23, as well as other proteins that are needed to create the rRNA transcripts and assemble the ribosome subunits.
It was originally thought that the only function of the nucleolus was to make and process rRNAs. However, recent experiments indicate that it also plays a role in gene silencing and cell cycle regulation. More specifically, the nucleoli appear to act as a storage area for several proteins such as ARF and cdc14p that are released at a certain time to affect the cell cycle.
The amount and size of nucleoli vary greatly between species and between the type of cells and their condition. Cells that have a higher level of protein synthesis require more ribosomes and therefore generally have larger and more numerous nucleoli. For example, mammalian nuclei can contain between one to four nucleoli, and the nucleoli can take up to 25% of the total volume of the nucleus. Changes in nucleoli size are largely due to changes in the granular center region. The nucleolus also undergoes changes during the cell cycle. As the cell approaches mitosis the nucleoli get smaller and eventually vanish. During mitosis there is little rRNA or protein synthesis so the nucleoli are not needed. After mitosis is finished rRNA synthesis restarts and the nucleoli reappear.
- Molecular Biology of the Cell, Alberts, third edition, 1994