L.5 RNA STRUCTURE

COURSE OUTLINE

• I. RNA STRUCTURE
  • A. Primary Structure
  • B. Secondary Structure
  • C. Tertiary Structure
• II. MAJOR CLASSES OF RNA
  • A. Messenger RNA (mRNA)
  • B. Ribosomal RNA (rRNA)
  • C. Transfer RNA (tRNA)
• III. EUKARYOTIC SMALL RNAs
  • A. Small Cytoplasmic RNAs (scRNAs)
  • B. Small Nuclear RNAs (snRNAs)
• IV. SUMMARY

I. RNA STRUCTURE

• RNA is an unbranched polymeric structure.
• Composed of mononucleotides joined together by phosphodiester bonds.
• Most RNAs exist as single strands capable of folding into complex structures.
• Three major types of RNA that participate in protein synthesis:
  • rRNA
  • tRNA
  • mRNA
  • These differ in terms of size, function, and structural modifications.

Differences from DNA

• Size: RNA is considerably smaller than DNA.
• Sugar: RNA contains ribose sugar (instead of deoxyribose).
• Nucleotide: RNA contains uracil (instead of thymine).
• Form: RNA usually exists in a single-strand form.

Table 1. Comparison of DNA and RNA

A. PRIMARY STRUCTURE

• RNA is initially synthesized as a single-stranded polymer by the process of transcription.
• Ribonucleotides are linked into a polar molecule by phosphodiester bonds.
  • Phosphodiester Bonds are formed between:
  • 3’-hydroxyl on the sugar of one ribonucleotide through a phosphate to the 5’-hydroxyl on the sugar of another ribonucleotide.
• Sugar-Phosphate Linkages:
  • Form a symmetrical backbone.
  • The 5’-end of one sugar linked through a phosphate to the 3’-end of the adjacent sugar.
• Bases are variable and stick out from the backbone.

B. SECONDARY STRUCTURE

• Double-Stranded RNA is single-stranded but can form regions of double helix by folding back on itself.
• Base Pairing: Complementary RNA sequences can be base pairs.
  • Examples:
  • Adenine with Uridine
  • Guanine with Cytosine
• A-Form Helix:
  • 2’-hydroxyl groups on the ribose sugar sterically hinder the formation of B form, causing double helical regions to assume conformations resembling A-DNA.
  • Nature of RNA double helix is similar to DNA.
  • Strands must be antiparallel.
• DNA-RNA Hybrids show A-form conformations.
• Other Structures: Varied shapes arise from various sections of RNA forming double-stranded regions via specific base pairing.
  • 5S Ribosomal RNA (rRNA) consists of helices, hairpin loops, internal loops, and bulges.
  • Transfer RNA (tRNA) achieves a compact shape due to base pairing and extensive stacking interactions.

C. TERTIARY STRUCTURE

Roles of Some RNAs

• Structural: Interact extensively with specific proteins.
• Catalytic functions: RNA can form very complex structures.

1. RNA Modifications

• Occur after RNA synthesis, including terminal additions and base modifications.
  • Methylations:
  • Occur at numerous positions of different bases.
  • Most common modifications allowing for unusual base pairings, enhancing RNA structural diversity.
  • Trimming, internal segment removal, and splicing also happen after RNA synthesis to convert inactive primary transcript into functional molecules.
  • Transfer RNA is the most heavily modified type of RNA.

II. MAJOR CLASSES OF RNA

• Three functionally distinct classes of RNA produced in prokaryotes.
• Four classes produced in eukaryotes.

A. MESSENGER RNA (mRNA)

• Most heterogeneous type in terms of size (500-6000 nucleotides).
• Carries genetic information from DNA to the cytosol and ribosomes, serving as a template for protein synthesis.
• Transcript of DNA.
• mRNA and DNA are nearly identical, except uracil replaces thymine.
• Being the largest type, mRNA contains multiple coding regions (exons).

1. PROKARYOTIC mRNA

I. Basic Features

• Not all portions code for polypeptides.
• Polycistronic: Carries information for the production of multiple polypeptides (cistrons); sequences that code for proteins.
• Leader Sequence/5’-Untranslated Region (5’-ULR): Contains sequences that are never translated into protein.
• Trailer Sequence/3’-Untranslated Region (3’-UTR): Contains sequences that are never translated into protein.
• Intercistronic Regions/Spacers: Sequences between cistrons.

II. Abundance

• Accounts for 5% of total cellular RNA.

III. Stability

• Stable for just a few minutes; has a short lifetime.

2. EUKARYOTIC mRNA

I. Basic Features

• Monocistronic: Carries information for the production of a single polypeptide; has only one coding region.
• Precursor Form: Heterogeneous nuclear RNA (hnRNA); most eukaryotic mRNA arises from post-transcriptional processing of large precursors.
• Identical to DNA; contains all genetic information, with sequences of the DNA.
• Includes leader sequence (5’-ULR) and trailer sequence (3’-UTR).
• Polyadenylate (Poly-A) Tail:
  • Long adenylate residues (200-300) at the 3’-end of the RNA chain.
  • Unique to eukaryotes; helps differentiate eukaryotic mRNA from prokaryotic mRNA.
• Cap:
  • Located at the 5’-end of eukaryotic mRNAs. Consists of a 7-methylguanylate molecule attached backward through a 5’ to 5’ triphosphate linkage.

II. Abundance

• No more than 5% of total cellular RNA.
• Precursor hnRNA accounts for approximately 7% of total cellular RNA.
• Fully processed mRNA accounts for about 3% of total cellular RNA.

III. Stability

• Relatively stable; half-lives of hours to days.

B. RIBOSOMAL RNA (rRNA)

• Ribosomes are complex structures and serve as the site of protein synthesis.
• Found in association with various proteins as components of the ribosomes.
• Ribosomal RNA combines with proteins to form ribosomes, where protein synthesis occurs.
• Contributes to 50% of ribosomal mass (most abundant).

a. Functions

• Structural: Provides a framework for ribosomes.
• Ribozyme: Acts as a catalyst for some translation reactions.
  • An RNA molecule that acts like an enzyme, aiding in speeding up certain reactions, such as forming peptide bonds between amino acids during protein synthesis.

1. PROKARYOTIC rRNA

I. Basic Features

• 23S rRNA: 2904 nucleotides, component of the large 50S ribosomal subunit.
• 16S rRNA: 1541 nucleotides, component of the small 30S ribosomal subunit.
• 5S rRNA: 120 nucleotides, component of the large 50S ribosomal subunit.

II. Abundance

• rRNA is the most abundant type of RNA.
• Comprises 80% of total prokaryotic cellular RNA.

2. EUKARYOTIC rRNA

• Generally larger than prokaryotic rRNA due to the increased size and complexity of eukaryotic ribosomes (80S) compared to prokaryotic ribosomes (70S).

I. Basic Features

• 28S rRNA: 4718 nucleotides; component of the large 60S ribosomal subunit.
• 18S rRNA: 1874 nucleotides; component of the small 40S ribosomal subunit.
• 5.8S rRNA: 160 nucleotides; component of the large 60S ribosomal subunit.
• 5S rRNA: 120 nucleotides; component of the large 60S ribosomal subunit; transcription product of a separate gene.

II. Abundance

• 4% of total eukaryotic cellular RNA is 40S precursor rRNA (an unfinished form).
• 71% is fully processed rRNAs (ready for ribosome assembly).

C. TRANSFER RNA (tRNA)

• Smallest RNA type (4S) with 74-95 nucleotide residues.
• There is one specific tRNA type for each amino acid.
• Contains unusual bases (e.g., pseudouracil).
• Exhibits extensive intrachain base pairing.
• Functions as an adaptor molecule carrying a specific amino acid (covalently attached to its 3’-end) to the site of protein synthesis, facilitating incorporation of amino acids into newly synthesized proteins in a template-dependent manner.
• Comprises approximately 15% of total RNA in the cell.

1. PROKARYOTIC tRNA

I. Basic Features

• Size: Small; average of 80 nucleotides.
• Structure: All tRNAs exhibit common structural features for ribosome function. Unique structural features are necessary for recognition by the enzyme that catalyzes amino acid attachment to tRNAs. Each tRNA has a unique sequence for pairing with appropriate codons in the ribosome.
• Processing: tRNAs arise from the processing of large precursor tRNAs.
• Modification: Heavily modified post-transcriptionally.

II. Abundance

• Accounts for approximately 15% of total cellular RNA.

2. EUKARYOTIC tRNA

I. Basic Features

• Size: Similar to prokaryotes in size and structural features.
• Modification: Heavily modified post-transcriptionally.

II. Abundance

• Accounts for approximately 15% of total cellular RNA.

III. EUKARYOTIC SMALL RNAs

• Serve a variety of functions and are classified into two broad types according to location.

A. Small Cytoplasmic RNAs (scRNAs)

• 7S RNA: Major scRNA with 294 nucleotides; RNA component of signal recognition particles.

B. Small Nuclear RNAs (snRNAs)

• Associated with proteins in small nuclear ribonucleoprotein particles (snRNPs).
  • snRNPs are involved in the splicing reactions needed to process heterogeneous nuclear RNA (hnRNA) into mature mRNA.

IV. SUMMARY

Table 2. Types of RNA

Reference(s)

• Jandoc, B. (January 2025). RNA Structure [PPT].
• Ferrier, D. R. (2014). Biochemistry. Lippincott Williams & Wilkins.