Protein synthesis, known as translation, converts genetic instructions carried by messenger RNA (mRNA) into functional proteins. The cellular machine responsible for this task is the ribosome, a complex structure found in all living organisms. Ribosomal RNA (rRNA) is the major component of the ribosome, distinguishing it from other RNA types like mRNA, which provides the blueprint, and transfer RNA (tRNA), which delivers the building blocks. This non-coding RNA molecule is central to the process, serving multiple roles from forming the physical structure to performing the chemical reaction that links amino acids together.
rRNA as the Structural Scaffold of the Ribosome
Ribosomal RNA molecules are responsible for the overall architecture of the ribosome, forming the foundational framework upon which ribosomal proteins are built. The ribosome is composed of two primary parts, a large subunit and a small subunit, and rRNA dictates the shape and size of both. rRNA accounts for approximately 60% of the ribosome’s mass. The rRNA folds into complex, highly stable three-dimensional shapes through extensive internal base pairing within its single strand.
These folded rRNA structures create a stable scaffold that interacts tightly with ribosomal proteins using various chemical bonds, maintaining the overall integrity of the entire machine. In prokaryotic cells, the ribosome is designated as 70S, consisting of a 30S small subunit (16S rRNA) and a 50S large subunit (23S and 5S rRNA). Eukaryotic cells possess larger 80S ribosomes, with an 18S rRNA in the 40S small subunit and 28S, 5.8S, and 5S rRNA molecules in the 60S large subunit.
Directing the Flow of Genetic Information
rRNA plays a direct logistical role in organizing the components required for protein assembly. The small subunit, with its core of rRNA, is responsible for the accurate decoding of the genetic message carried by the mRNA. It ensures that the incoming transfer RNA (tRNA) molecule correctly pairs its anticodon sequence with the complementary codon sequence on the mRNA template. This action maintains the precise reading frame necessary for the production of the correct protein sequence.
The three primary binding sites within the ribosome—the A, P, and E sites—are formed predominantly by the intricate three-dimensional structure of the rRNA. These sites are positioned to cradle the mRNA strand and sequentially accommodate the tRNA molecules during elongation. The A (aminoacyl) site is the entry point for the new tRNA, the P (peptidyl) site holds the tRNA attached to the growing polypeptide chain, and the E (exit) site is where the spent tRNA is discharged. The rRNA framework controls the precise alignment and movement of these molecules, guiding the complex through translocation, where the ribosome shifts three nucleotides down the mRNA strand.
Catalyzing Peptide Bond Formation
The function of rRNA is its direct involvement in the chemical reaction that creates the protein chain. The large ribosomal subunit is the site of this reaction, and the rRNA within it functions as a ribozyme, an RNA molecule possessing catalytic activity. This catalytic role is known as peptidyl transferase activity, located in a specialized region of the large subunit’s rRNA. The peptidyl transferase center is formed entirely by the rRNA; the nearest ribosomal protein is too far away to participate directly in the chemistry.
This catalytic activity involves the formation of a peptide bond, which links the carboxyl group of the amino acid in the P site and the amino group of the amino acid in the A site. The rRNA facilitates the reaction by precisely positioning the two substrate tRNA molecules. This accurate positioning reduces the entropic barrier and stabilizes the transition state of the reaction, accelerating the rate of peptide bond formation by many orders of magnitude.
Biological Significance and Targeting
The structure and function of ribosomal rRNA are conserved across all life forms, yet small differences exist between prokaryotic and eukaryotic ribosomes. This variation in rRNA sequence and structure, particularly between bacterial (70S) and human (80S) ribosomes, is leveraged in medicine. These structural discrepancies allow compounds to selectively interfere with bacterial protein synthesis without disrupting the host cell’s machinery.
Many commonly used antibiotics function by binding to specific regions of bacterial rRNA, thereby inhibiting translation. For instance, aminoglycoside antibiotics, such as streptomycin, bind to the 16S rRNA in the small bacterial subunit, causing errors in the reading of the mRNA code. Other antibiotics target the 23S rRNA in the large subunit, directly blocking the peptidyl transferase activity and halting polypeptide chain growth.