Ribosomal RNA (rRNA) - RNA / BOC Sciences

What is rRNA?

Ribosomal RNA (rRNA) is the most abundant RNA in the cell, accounting for more than 85% of total RNA. rRNA has defined species and conserved nucleotide sequences. rRNA does not perform its function when it exists alone, but when combined with a variety of proteins to form ribosomes, it can read the genetic information contained in the tRNA nucleotide sequences and translate them into sequences of amino acids in proteins. rRNA, together with ribosomal proteins, constitutes the ribosome, which recruits mRNAs, tRNAs, and a variety of protein factors necessary for protein biosynthesis and provides an essential site for protein biosynthesis. synthesis of proteins.

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rRNA Structure

In prokaryotes, ribosomes consist of about 40% protein and 60% rRNA. The eukaryotic ribosome consists of three or four rRNA molecules and about 80 different proteins. Its molecular weight is about 4,200,000 Da. About two-thirds of the material is ribosomal RNA, and one-third of it is different ribosomal proteins. Ribosomes are not membrane-bound organelles. Each ribosome consists of two subunits, a larger subunit and a smaller subunit; both are RNA-protein complexes. The larger subunit has catalytic activity, while the smaller subunit acts as a decoder. The names of the subunits are based on their sedimentation rate, which means how fast they can settle down when the cell lysis mixture is spanned in a centrifuge. The rate is measured in Svedberg units (S) rather than size. This is why the names of the subunits do not add up. For example, the bacterial 70S ribosome consists of a large 50S and a small 30S subunit, while the human 80S ribosome contains 60S and 40S subunits.

Small Subunit (Prokaryotic 30S/Eukaryotic 40S)

It consists of a 16S or 18S rRNA molecule, which is the RNA component of the ribosome.
It contains multiple proteins that help stabilize the rRNA structure and participate in catalytic reactions.
In eukaryotes, the small subunit also includes a 5S rRNA molecule.

Large Subunit (Prokaryotic 50S/Eukaryotic 60S)

It consists of a 23S rRNA, a 5S rRNA (eukaryotes), and a 5.8S rRNA molecule.
It contains a variety of proteins that are involved in the formation of the active site and maintenance of ribosome structure.
It contains the peptidyltransferase center (PTC), a key catalytic region for protein synthesis.

Schematic diagram of ribosomal RNA(rRNA). The process of protein translation through the ribosome.

Types of rRNA

Based on the size and function, rRNA has been further classified into different types. The major types of rRNA in prokaryotes are:

16S rRNA: Located in the 30S small ribosomal subunit, it is crucial for mRNA binding and translation initiation.
23S rRNA: Found in the 50S large ribosomal subunit, it is involved in peptide bond formation.

Eukaryotic rRNA types include:

18S rRNA: Part of the 40S small ribosomal subunit, essential for mRNA binding and translation initiation.
28S rRNA: In the 60S large ribosomal subunit, plays a role in peptide bond formation.
5.8S rRNA: Associates with 28S rRNA in the large subunit.
5S rRNA: Located in the large ribosomal subunit, contributes to ribosomal structure and function.

Both 16S and 18S rRNA are key to mRNA recognition and binding, while the catalytic activity of the ribosome is mediated by 23S bacteria or 28s eukaryotes. For example, in prokaryotes, 16S rRNA is a component of small ribosomal subunits and 23S rRNA is a component of large subunits involved in mRNA decoding and peptide bond formation. Eukaryotic ribosomes, on the other hand, are more complex and have an additional rRNA type of 5.8S rRNA(5S rRNA in some cases) to allow for their complex regulatory functions.

Function rRNA

rRNA also creates a much needed skeleton for construction around the ribosome, so it can move ribosomal proteins and mrnas correctly. It also facilitates the translation process by aligning mRNA and tRNA, which are used for protein synthesis.

Mechanism of rRNA in Translation

During translation, rRNA facilitates the interaction of mRNA and tRNA at the ribosome interface for proper localization in the ribosome body. While 16S and 18S rRNAs are responsible for mRNA decoding, crucially, the large subunits of ribosomes in bacteria or fungi, which have the function of catalyzing peptide bond formation. These are vital physiological processes when it comes to translation.

Interaction with Ribosomal Proteins and mRNA

rRNA associates with proteins of the ribosome to form a composite structure, termed as ribonucleoprotein( RNP) which make up the larger part of complete 70S or polyribosomal apparatus. They are essential for S ribosome structure and function. Moreover, rRNA plays a crucial role in the interaction with mRNA and tRNA during translation process, resulting hereby that accurate protein synthesis.

What is the Difference Between a Ribosome and Ribosomal RNA?

The ribosome is built around the core structure rRNA, and the ribosomal protein binds to the RNA. This assembly process, in turn, includes the synthesis and processing of rRNA, and the binding of ribosomal proteins to build functional subunits.

Ribosome: A functional molecular machine made up of rRNA and ribosomal proteins, responsible for protein synthesis.
rRNA: A component of the ribosome that provides structural support and participates in ribosomal function but does not function independently.

The ribosome operates as a complete entity for translating mRNA into proteins, whereas rRNA is a critical structural and functional component of the ribosome. rRNA forms the scaffold for ribosome assembly and plays a key role in the ribosomal activity of translation. Without rRNA, the ribosome would be nonfunctional.

Roles of rRNA in Disease

The ribosomal RNA (rRNA) is an essential component of the structure and function of the ribosome, its dysregulation are therefore linked to a range of diseases. These events have mild to severe disruptions in cellular protein synthesis and could be possibly attributed with initiation of various pathological conditions. Mutations or misregulation of rRNA can drastically affect ribosome performance, and result in a variety of disorders known as the ribosomopathies. Some of these diseases are attributed to ribosome biogenesis and function defects causing dysfunctional RNPs that affects a variety of cellular processes.

Ribosomopathies: A group of disorders result from defects in ribosome biogenesis, which arise primarily owing to mutations that occur within rRNA genes or those involved with rRNA processing. Dysfunctional ribosomes disturb protein synthesis and result in a wide range of clinical features.
RNA Processing Disorders: Mutations in genes responsible for the processing of rRNA into mature forms produce dysfunctional ribosomes if defects hamper this essential step. These defects underlie conditions such as Diamond-Blackfan anemia and other hematological diseases.

Examples of Diseases Associated with rRNA

Cartilage–Hair Hypoplasia (CHH)

Cause: Mutations in the RMRP gene, which encodes a small RNA involved in rRNA processing.
Impact: This condition affects rRNA processing, leading to defective ribosome assembly and resulting in dwarfism, immune deficiencies, and other developmental abnormalities.

North American Indian Childhood Cirrhosis (NAIC)

Cause: Mutations in the CIRH1A gene, which is involved in rRNA processing and ribosome biogenesis.
Impact: The disorder is characterized by progressive liver disease due to impaired ribosome function and protein synthesis, leading to cirrhosis and other liver-related symptoms.

Dyskeratosis Congenita (DC)

Cause: Mutations in genes involved in telomere maintenance and rRNA processing, such as DKC1.
Impact: This genetic disorder affects rRNA processing and telomere maintenance, leading to symptoms including skin abnormalities, oral leukoplakia, and bone marrow failure.

Shwachman-Diamond Syndrome (SDS)

Cause: Mutations in the SBDS gene, which is essential for rRNA processing and ribosome biogenesis.
Impact: This syndrome results in pancreatic insufficiency, hematological abnormalities, and skeletal defects due to defective ribosome assembly.

Potential of rRNAs as Therapy Targets

The understanding of rRNA's role in disease has opened avenues for potential therapeutic interventions. Strategies to address rRNA-related disorders include:

Gene Therapy: Correcting mutations in rRNA genes or genes involved in rRNA processing to restore normal ribosome function and protein synthesis.
RNA-based Therapies: Using small molecules or RNA molecules to correct defective rRNA or enhance its processing, aiming to improve ribosome assembly and function.
Targeted Drug Development: Designing drugs that specifically target the molecular pathways involved in rRNA processing and ribosome assembly, to mitigate the effects of rRNA-related diseases.
Protein Replacement Therapies: Developing therapies to replace or enhance defective ribosomal proteins that interact with rRNA, potentially compensating for rRNA processing defects.