Ribosomal RNA and Ribosome Biogenesis

Ribosomal RNA is the structural and catalytic heart of the ribosome, the machine that translates messenger RNA into protein. Far from being a passive scaffold, rRNA forms the catalytic centre that joins amino acids, making the ribosome a ribozyme. Building a ribosome—ribosome biogenesis—requires transcribing, processing, modifying, and folding rRNA and assembling it with dozens of proteins.

Definition

Ribosomal RNA is the RNA component of the ribosome that provides both its structural framework and its peptidyl-transferase catalytic activity; ribosome biogenesis is the coordinated transcription, processing, modification, and assembly of rRNA with ribosomal proteins to form functional subunits.

Scope

This topic covers the role of rRNA as the core of the ribosome, the catalytic (peptidyl-transferase) activity it provides, and the pathway of ribosome biogenesis: rRNA transcription, processing and modification, and assembly of the small and large subunits, much of it organised in the nucleolus. It is reference-educational and does not give clinical guidance.

Core questions

• Why is the ribosome considered a ribozyme rather than a protein enzyme?
• How is ribosomal RNA transcribed, processed, and modified?
• How are the small and large ribosomal subunits assembled from rRNA and proteins?
• How is ribosome production coordinated with cellular growth?

Key concepts

• Ribosomal RNA as catalytic core
• Peptidyl-transferase centre
• Small and large ribosomal subunits
• rRNA transcription and processing
• rRNA chemical modification
• Nucleolus as assembly site
• Ribosome biogenesis and cell growth

Key theories

The ribosome is a ribozyme

High-resolution structures of the large ribosomal subunit showed that the peptidyl-transferase centre is composed of RNA, with no protein at the catalytic site, establishing that rRNA itself catalyses peptide-bond formation.

Mechanisms

Most ribosomal RNA is transcribed as a long precursor that is cleaved, trimmed, and chemically modified at many positions, then folded and assembled with ribosomal proteins into the small and large subunits, a process organised largely within the nucleolus and assisted by numerous accessory factors and small nucleolar RNAs. Atomic structures of the large subunit revealed that the active site where peptide bonds form is built from rRNA, not protein, so the ribosome is a ribozyme and its catalytic core is the RNA itself. The two subunits then act together during translation, with the rRNA coordinating tRNA positioning and catalysis. That rRNA precursors can contain self-splicing introns provided early evidence that RNA can perform its own processing chemistry.

Clinical relevance

Defects in ribosome biogenesis underlie a group of disorders (ribosomopathies), the nucleolus and rRNA synthesis are studied in relation to cell proliferation and cancer, and rRNA is a major target of antibiotics. This entry presents that biology as educational background and is not a basis for individual diagnosis or treatment.

History

Long debated as either a protein- or RNA-catalysed machine, the ribosome's mechanism was settled when atomic-resolution structures of the large subunit placed only RNA at the peptidyl-transferase centre, confirming that rRNA is the catalyst. This built on the earlier recognition of catalytic RNA and reframed ribosome biogenesis as the construction of a large RNA-based enzyme.

Key figures

• Thomas Steitz
• Ada Yonath
• Venkatraman Ramakrishnan
• Harry Noller

Seminal works

• ban-2000
• nissen-2000
• kruger-1982

Frequently asked questions

Why is the ribosome called a ribozyme?

Because its catalytic centre, where peptide bonds are formed, is made of ribosomal RNA rather than protein, so the RNA itself catalyses the reaction.

Where are ribosomes assembled in the cell?

Much of ribosome biogenesis—rRNA transcription, processing, and early assembly with proteins—takes place in the nucleolus before the subunits are exported to the cytoplasm.