The nucleolus is a structure found within the nucleus of eukaryotic cells, and the answer to whether it is membrane-bound is “no.” Unlike many other cell compartments, such as the mitochondria or the endoplasmic reticulum, the nucleolus is a non-membrane-bound organelle. It exists as a distinct, specialized region within the nucleus without a lipid bilayer separating it from the surrounding nucleoplasm. Its components self-organize, enabling its primary function as the cell’s ribosome factory.
Defining the Nucleolus
The nucleolus is a structure found inside the nucleus of a eukaryotic cell. Its size is not fixed; it can grow considerably in cells that require high levels of protein synthesis, sometimes occupying up to 25% of the total nuclear volume. Under a microscope, the nucleolus appears as a dense, dark spot, indicating the high concentration of molecules packed within its boundaries.
This concentrated body is composed mainly of three types of macromolecules: ribosomal DNA (rDNA), ribosomal RNA (rRNA), and proteins. The rDNA provides the genetic blueprint, while the rRNA is the active transcript, and the proteins include enzymes and assembly factors necessary for its function.
The Structural Organization of a Non-Membrane Bound Organelle
The lack of a surrounding membrane raises the question of how the nucleolus maintains its distinct shape and composition within the nucleus. The mechanism responsible for this organization is known as Liquid-Liquid Phase Separation (LLPS). This process is similar to how oil separates from water, causing specific molecules to concentrate and “demix” from the rest of the nucleoplasm to form a dense, liquid-like droplet.
LLPS allows the nucleolus to be a highly dynamic structure, where molecules can rapidly enter and exit, while the overall compartment remains intact. The internal organization of the nucleolus is characterized by three main morphological zones, which correspond to progressive stages of its activity. These zones are the Fibrillar Centers (FCs), the Dense Fibrillar Component (DFC), and the Granular Component (GC).
The Fibrillar Centers contain the ribosomal DNA genes, serving as the blueprint for ribosome components. Surrounding the FCs is the Dense Fibrillar Component, which is the region where the initial transcription of the ribosomal RNA genes occurs. Finally, the Granular Component is the outermost zone and is characterized by the accumulation of newly formed, yet immature, ribosomal particles that are awaiting export.
Primary Function: Ribosome Production
The primary biological role of the nucleolus is to serve as the cell’s factory for building ribosomes, the machinery responsible for protein synthesis. This production begins at specific chromosomal locations called Nucleolar Organizing Regions (NORs), where the genes for three of the four types of ribosomal RNA are located. These genes are actively transcribed by RNA polymerase I, which generates a large precursor molecule of ribosomal RNA.
Following transcription, the long precursor rRNA molecule must be processed and modified, a stage that begins within the Dense Fibrillar Component. This processing involves numerous small nucleolar RNAs (snoRNAs) and proteins that precisely cut and chemically alter the rRNA to yield the mature 5.8S, 18S, and 28S rRNA strands. The final stage of assembly takes place in the Granular Component, where the processed rRNA is combined with ribosomal proteins.
These ribosomal proteins are synthesized in the cytoplasm and must be imported back into the nucleus for assembly. The rRNA and ribosomal proteins are brought together to form the large (60S) and small (40S) ribosomal subunits. Once assembly is complete, these subunits are transported out of the nucleus and into the cytoplasm, where they combine to form a complete, functional ribosome capable of translating messenger RNA into proteins.