Where are ribosomes synthesized?

Ribosomes are primarily synthesized in the nucleolus of eukaryotic cells, where ribosomal RNA is transcribed and preribosomal subunits are assembled before export to the cytoplasm for final maturation into functional particles, while in prokaryotes ribosomes are assembled in the cytoplasm from nascent rRNA and ribosomal proteins.

Core location

The nucleolus is a prominent subnuclear compartment dedicated to the early stages of ribosome biogenesis, including transcription of large rRNA precursors by RNA polymerase I and initial assembly of ribosomal proteins onto pre-rRNA scaffolds. In eukaryotes, ribosome synthesis thus spans the nucleolus for rRNA production and assembly, and the cytoplasm for late maturation steps that finalize the small and large subunits. By contrast, bacteria and other prokaryotes lack a nucleus and nucleolus, so ribosome assembly occurs in the cytoplasm directly on rRNA transcribed from rDNA operons.

Molecular steps

Ribosome biogenesis begins with high-output rDNA transcription in nucleolar organizer regions by RNA polymerase I, producing a 35S/47S pre-rRNA that is processed into the mature 18S, 5.8S, and 28S/25S rRNAs for small and large subunits, respectively. Concurrently, the 5S rRNA is transcribed by RNA polymerase III, typically in the nucleoplasm and then integrated into the large subunit assembly pathway; many Pol III products, including 5S, traffic to the cytoplasm as part of ribonucleoprotein complexes. Ribosomal proteins are translated in the cytoplasm and imported into the nucleus and nucleolus, where they bind nascent pre-rRNAs to form preribosomal particles that undergo successive processing and structural remodeling.

Nucleolar organization

Within the nucleolus, ribosome synthesis proceeds in a spatially ordered manner: transcription occurs in fibrillar centers and dense fibrillar components, while assembly and maturation proceed in the granular component before nuclear export. Multiple trans-acting factors—snoRNPs for site-specific 2′-O-methylation and pseudouridylation, helicases, AAA-ATPases, GTPases, and specialized assembly factors—coordinate pre-rRNA processing and RNP remodeling. These steps are tightly cell-cycle regulated, with rDNA transcription peaking in S/G2, silencing in mitosis, and rapid reactivation thereafter to meet translational demand.

Export and cytoplasmic maturation

Pre-40S and pre-60S subunits are exported from the nucleolus to the nucleoplasm and then through nuclear pores to the cytoplasm, where final rRNA cleavages and conformational “proofreading” yield competent subunits. For the small subunit, cleavage of 20S pre-rRNA to mature 18S occurs in the cytoplasm, coupled to kinase-regulated factor release and structural beak formation; analogous late steps complete the large subunit. This biphasic geography—nucleolar assembly followed by cytoplasmic maturation—ensures quality control before subunits engage in translation.

Energetic and regulatory burden

Ribosome biogenesis is among the most energy-intensive processes in growing cells, consuming a substantial fraction of transcriptional capacity and metabolic resources to synthesize and process rRNAs and assemble them with dozens of ribosomal proteins. Its rate is coupled to nutrient and growth signaling; perturbation of nucleolar function or rRNA synthesis triggers stress responses, underscoring the nucleolus as a sensor as well as a factory. The spatial separation of rRNA synthesis (nucleolus) from cytoplasmic late maturation also integrates nuclear transport checkpoints with biosynthetic demand.