Nucleolus

For medical students2 min readUpdated 2026-10-10

The nucleolus is the densest and typically most prominent spherical structure within the cell nucleus. It is not a membrane-bound organelle, but rather a specialized chromatin condensate dedicated to massive macromolecular assembly for cellular protein synthesis.

NatureNot an organelle, but a functional chromatin derivative

Localization (NORs)Secondary constrictions of chromosomes 13, 14, 15, 21, and 22

HistochemistryStains magenta/pink with the Brachet reaction (targeting RNA)

UltrastructureComposed of fibrillar centers/amorphous, dense fibrillar, and granular components

Genetic Basis: Nucleolar Organizer Regions

The formation of the nucleolus does not occur at random sites within the nucleus, but rather at specific chromosomal loci known as nucleolar organizer regions (NORs). Structurally, these are clusters consisting of multiple copies of genes encoding ribosomal RNAs.

Humans have exactly 10 NORs located at the secondary constrictions of five pairs of chromosomes: 13, 14, 15, 21, and 22.

Genetic Content: These zones concentrate the genes for three types of rRNA (28S, 18S, and 5.8S). They are grouped into a single cluster and transcribed together as a single unit. Notably, the gene for the fourth type of rRNA (5S) is located and transcribed completely separately.
Copy Number: Estimates suggest there are anywhere from 200 to over a thousand copies of these genes per haploid genome.
Structural Dynamics: Despite the presence of 10 organizers, a single nucleus rarely contains exactly 10 distinct nucleoli. Due to clustering, these regions can fuse into a single large nucleolus or disperse into multiple groups. Consequently, the visible number of nucleoli is variable.

Functional Activity: From Transcription to Assembly

The nucleolus functions as a assembly line for producing ribosomal components. This process can be divided into three sequential stages:

Transcription: Continuous, highly active synthesis of a single long precursor molecule—pre-rRNA—takes place at the gene clusters within the NORs. This molecule contains nucleotide sequences for three future types of ribosomal RNA.
Processing (Maturation): Inside the nucleolus, the single precursor transcript is cleaved into separate functional rRNA molecules, which undergo necessary chemical modifications. Simultaneously, pre-5S rRNA is produced and processed.
Subunit Assembly: Mature rRNA molecules combine with specialized ribosomal proteins. These proteins are not synthesized in the nucleus; they are imported from the cytoplasm. This interaction forms completed ribosomal subunits, which then leave the nucleus and travel back to the cytoplasm to participate in translation.

Nucleolar Ultrastructure

Electron microscopy reveals that nucleolar morphology is strictly tied to its functions. Three key structural components are distinguished:

Amorphous component: Reflects the genetic base; these are the chromatin regions (DNA of the nucleolar organizers) physically associated with the nucleolus.
Fibrillar component: Reflects the transcription process, consisting of fine RNA strands (synthesized pre-rRNA and mature rRNAs).
Granular component: Reflects the assembly stage, appearing as clusters of small granules—maturation-stage ribosomal subunits.

Light Microscopy Identification

Nucleoli have high optical density, making them easily visible even with routine histological stains.

However, for specific identification, a specialized histochemical method is used—the Brachet reaction. This method selectively stains RNA. Because the concentration of ribosomal RNA and its precursors is extremely high in the nucleolus, it stains a rich, intense magenta color against the lightly stained background of the rest of the nucleus.

Mnemonic

To remember the chromosome pairs with nucleolar organizers (13, 14, 15, 21, 22), note the sequence: three consecutive numbers from 13 to 15, and two consecutive numbers from 21 to 22.

Frequently asked questions

Where and on which chromosome is the 5S rRNA gene transcribed?

The 5S rRNA gene is located and transcribed separately from the main cluster of rRNA genes (28S, 18S, 5.8S). Its precise chromosomal location is distinct, and pre-5S rRNA formation occurs concurrently with the processing of other rRNA precursors.

During which phases of the cell cycle (mitosis) does the nucleolus disappear and reappear?

The nucleolus disassembles during prophase and reappears during telophase. These structures are transient, with dynamics tied to cell division:

Prophase: Nucleoli shrink, fragment, and completely disappear by the end of the period.
Telophase: New nucleoli are reconstructed and formed.

What specific proteins and RNP complexes carry out pre-rRNA processing in the nucleolus?

Fibrillarin serves as a marker protein of the fibrillar component involved in rRNA processing. The fibrillar component also contains rRNAs and ribonucleoproteins, alongside RNA polymerase I, transcription factors, and nucleases.

Is the nucleolus a membrane-bound organelle?

No, the nucleolus is not an independent organelle. It is a dense chromatin derivative lacking its own membrane.

Why can cells of the same type have a variable number of nucleoli?

There are 10 nucleolar organizers in the nucleus. They can fuse into a single large cluster or form multiple groups, causing the microscopically visible number of nucleoli to fluctuate.

Where do proteins for ribosome assembly come from?

Ribosomal proteins are not synthesized inside the nucleus. They are produced in the cell cytoplasm and subsequently imported into the nucleolus to join mature rRNAs.

What does the Brachet reaction stain, and what color does it yield?

The Brachet reaction specifically detects RNA. Due to the massive amount of rRNA, nucleoli stain a bright magenta color.

Go deeper

Molecular mechanisms of pre-rRNA transcription
Processing and chemical modification stages of ribosomal RNA
Transport of ribosomal subunits through nuclear pores into the cytoplasm
Structure and function of 5S rRNA
Correlation between nucleolar activity and cellular protein synthesis rates