- The nucleolar organizer region (NOR) is a chromosomal locus that plays a central role in the formation of the nucleolus and the production of ribosomes in eukaryotic cells.
- NORs contain clusters of tandemly repeated ribosomal DNA (rDNA) genes, which encode the precursor ribosomal RNA (pre-rRNA) transcripts essential for ribosome biogenesis. These regions are the foundation upon which nucleoli assemble and are therefore critical for cellular growth and protein synthesis.
- In humans, NORs are located on the short arms (p arms) of five acrocentric chromosomes: 13, 14, 15, 21, and 22. Each NOR consists of hundreds of repeated copies of a transcription unit that includes the sequences for 18S, 5.8S, and 28S rRNAs, interspersed with intergenic spacer regions. These rDNA repeats are transcribed by RNA polymerase I to produce the 47S pre-rRNA (in humans), which is then processed into the mature rRNAs that form the structural and functional core of ribosomes.
- During interphase, active NORs are the sites of intense transcriptional activity and serve as the organizational center of the nucleolus, a dynamic, membrane-less nuclear body dedicated to rRNA synthesis, processing, and ribosome assembly. The transcriptional activity of NORs attracts numerous nucleolar proteins and RNA processing factors, leading to the formation of the characteristic tripartite nucleolar structure: the fibrillar center (FC), dense fibrillar component (DFC), and granular component (GC). Each of these subdomains corresponds to distinct stages of rRNA transcription and processing.
- The functionality of NORs is not solely determined by their DNA sequence but also by their epigenetic status. Not all rDNA repeats are transcriptionally active at any given time; a proportion remains silent, and the balance between active and inactive repeats can shift depending on the cell’s metabolic needs, developmental stage, or stress conditions. Factors such as chromatin modifications, DNA methylation, and nucleolar transcription factors (e.g., UBF and SL1) influence NOR activity and, consequently, nucleolar size and number.
- Importantly, NORs also undergo structural changes during the cell cycle. In mitosis, rRNA transcription ceases, and the nucleolus disassembles. However, NORs remain visible as specific chromosomal regions and can be detected using silver staining techniques due to their association with particular proteins. As cells exit mitosis, transcription resumes at NORs, and nucleoli reform around these active sites, highlighting the NOR’s role as a nucleation point for nucleolar reassembly.
- In summary, nucleolar organizer regions are essential chromosomal domains that harbor rDNA gene clusters and orchestrate the biogenesis of the nucleolus. Through their transcriptional activity, NORs regulate ribosome production and, by extension, cellular growth and proliferation. Their dynamic regulation and central role in nucleolar formation underscore their importance in both normal physiology and disease contexts, such as cancer and developmental disorders.
