The Nucleolus: What Is It and What Does It Do in a Cell?

Cells are the fundamental units of life, and each contains a nucleus that houses the cell’s genetic blueprint. Inside the nucleus of eukaryotic cells—the cells that make up animals, plants, and fungi—lies a structure called the nucleolus. Though it appears as a dark spot under a microscope, the nucleolus is a bustling hub of activity. It is a specialized region that produces and assembles the machinery for building proteins, which is necessary for a cell’s ability to grow, function, and reproduce.

Locating the Nucleolus: A Key Player Inside the Cell

The nucleolus resides within the nucleus of eukaryotic cells, appearing as a dense, spherical body. Unlike many other organelles, the nucleolus is not enclosed by a membrane. This allows for a constant exchange of molecules with the surrounding nucleoplasm and enables it to behave like a dynamic liquid droplet, forming through liquid-liquid phase separation.

The appearance of the nucleolus is not static; it changes in response to the cell’s needs. A cell that is actively producing large amounts of protein has a larger and more prominent nucleolus. A cell can also have more than one nucleolus, and the number can fluctuate depending on its metabolic state. For instance, human cells can start with several small nucleoli that fuse into one or two larger ones as the cell matures.

Unpacking the Nucleolus: Structure and Components

The nucleolus possesses an organized internal structure, divided into three main regions: the Fibrillar Center (FC), the Dense Fibrillar Component (DFC), and the Granular Component (GC). These sub-compartments are not separated by membranes but represent areas where different stages of ribosome production occur. Each region has a unique composition of proteins and nucleic acids reflecting its role.

The Fibrillar Center is the innermost region and contains the genes for ribosomal RNA (rRNA). Surrounding the FC is the Dense Fibrillar Component, a denser area where newly made rRNA molecules are modified and processed.

The outermost region is the Granular Component, which appears granular under a microscope. This area is where processed rRNA molecules are assembled with ribosomal proteins imported from the cytoplasm to form pre-ribosomal subunits before they are exported.

The Nucleolus: The Cell’s Ribosome Production Hub

The primary function of the nucleolus is ribosome biogenesis—the process of manufacturing ribosomes. Ribosomes are the cell’s protein factories, translating genetic code from messenger RNA (mRNA) into the proteins needed for cellular activity. The nucleolus orchestrates this production line, which consumes a significant amount of the cell’s energy.

The process begins in the Fibrillar Center, where an enzyme transcribes ribosomal DNA (rDNA) into a precursor molecule called pre-rRNA. This pre-rRNA then moves into the Dense Fibrillar Component for modification and cleavage into the mature 18S, 5.8S, and 28S rRNA molecules.

In the final stage in the Granular Component, these mature rRNA molecules are assembled with ribosomal proteins. This assembly results in the formation of two pre-ribosomal units: the small (40S) and large (60S) subunits. These completed subunits are then exported from the nucleus to the cytoplasm, where they join to form a functional ribosome.

More Than Just Ribosomes: Diverse Functions of the Nucleolus

While ribosome production is its main task, the nucleolus is a multifunctional hub involved in other cellular processes. It plays a part in the cell’s response to stress. When a cell experiences adverse conditions like DNA damage or nutrient deprivation, the nucleolus can act as a sensor, triggering protective pathways and sequestering proteins to halt cell growth.

The nucleolus also contributes to the regulation of the cell cycle, the ordered sequence of events that leads to cell division. Certain proteins that control cell cycle progression accumulate in the nucleolus at specific stages, indicating its role in coordinating cell growth with division.

Furthermore, the nucleolus is involved in the assembly of other molecular complexes besides ribosomes, such as the signal recognition particle. Evidence also suggests it influences aging and genome organization.

The Nucleolus and Its Impact on Health and Disease

The role of the nucleolus in cell growth and protein production means that its dysfunction is linked to a range of human diseases. Cancer cells often have enlarged and irregularly shaped nucleoli. This is because the rapid proliferation of cancer cells requires a massive number of ribosomes to synthesize the proteins needed for growth, leading to a hyperactive and altered nucleolus.

Viral infections also involve the nucleolus, as many viruses hijack the nucleolar machinery to replicate. Viruses can manipulate proteins within the nucleolus to aid in the production of viral components or to disrupt the cell’s normal stress responses. For example, proteins like B23 can be used by viruses such as HIV and adenovirus to enhance viral replication.

Furthermore, specific genetic disorders, known as “ribosomopathies,” are caused by mutations in genes related to ribosome production. These conditions, such as dyskeratosis congenita, result from faulty ribosome biogenesis and can lead to a variety of symptoms. These connections have made the nucleolus a target for developing new therapeutic strategies.