RNA and the Genetic Code Notes

RNA and the Genetic Code

Introduction

  • Hepatitis C virus (HCV) leads to cirrhosis and liver failure.
  • HCV is commonly associated with intravenous drug use.
  • The virus causes ongoing damage and inflammation, leading to scar tissue formation that replaces normal liver cells.
  • Scar tissue buildup impairs liver function, eventually leading to liver failure.
  • Interferon, a peptide signal, is released by infected hepatocytes to combat the virus by interfering with viral replication.
  • Interferon curtails transcription and translation in virally infected cells.
  • Interferon induces the production of RNNase L, which cleaves RNA, further reducing viral replication.
  • Interferon acts as a defense mechanism against viral pathogens.
  • Transcription converts double-stranded DNA into single-stranded RNA.
  • Translation converts the nucleotide sequence into a protein.
  • Gene expression is controlled, leading to the differentiation of the totipotent zygote into various tissues.

The Genetic Code

  • Organisms must:
    • Store and preserve genetic information.
    • Pass information to future generations.
    • Express information to carry out life processes.
  • DNA and RNA use nitrogenous bases for coding.
  • Proteins are composed of amino acids.
  • The genetic code translates genetic information into proteins.
  • Proteins are essential for organism development and function.
  • The central dogma of molecular biology illustrates the transfer of genetic information.
  • A gene is a DNA unit encoding a specific protein or RNA molecule.
  • Genes are expressed through transcription and translation.
  • DNA replication, transcription, and translation are key processes.
  • Messenger RNA (mRNA) is synthesized in the 5' to 3' direction.
  • mRNA is complementary and antiparallel to the DNA template strand.
  • The ribosome translates mRNA from the amino terminus (N-terminus) to the carboxy terminus (C-terminus).

Types of RNA

  • Three main types of RNA:
    • mRNA
    • tRNA
    • rRNA
Messenger RNA (mRNA)
  • mRNA carries the amino acid sequence information to the ribosome.
  • mRNA is transcribed from template DNA strands by RNA polymerase enzymes in the nucleus.
  • mRNA undergoes post-transcriptional modifications before release from the nucleus.
  • mRNA contains information translated into protein.
  • mRNA is read in three-nucleotide segments called codons.
  • In eukaryotes, mRNA is monocistronic, translating into only one protein product.
  • In prokaryotes, mRNA may be polycistronic; translation at different locations can yield different proteins.
Transfer RNA (tRNA)
  • tRNA converts the language of nucleic acids to the language of amino acids.
  • Each tRNA molecule contains a folded RNA strand with a three-nucleotide anticodon.
  • The anticodon recognizes and pairs with the appropriate codon on mRNA in the ribosome.
  • There are 20 amino acids in eukaryotic proteins, each represented by at least one codon.
  • Amino acids are connected to specific tRNA molecules, which are then considered charged or activated.
  • Mature tRNA is found in the cytoplasm.
  • Each amino acid is activated by a different aminoacyl-tRNA synthetase, requiring two high-energy bonds from ATP.
  • Aminoacyl-tRNA synthetase transfers the activated amino acid to the 3' end of the correct tRNA.
  • Each tRNA has a CCA nucleotide sequence where the amino acid binds.
  • The high-energy aminoacyl-tRNA bond supplies the energy to create a peptide bond during translation.
Ribosomal RNA (rRNA)
  • rRNA is synthesized in the nucleolus.
  • rRNA functions as part of the ribosomal machinery during protein assembly in the cytoplasm.
  • Many rRNA molecules function as ribozymes (enzymes made of RNA molecules).
  • rRNA helps catalyze the formation of peptide bonds and is important in splicing out its own introns within the nucleus.

Codons

  • A codon is a three-letter unit that is translated into an amino acid.
  • Genetic code tables help determine the amino acid translated from each mRNA codon.
  • Each codon consists of three bases, resulting in 64 possible codons.
  • Codons are written in the 5' to 3' direction.
  • The code is unambiguous: each codon specifies only one amino acid.
  • 61 codons code for amino acids; 3 codons encode for termination of translation.
  • The genetic code is universal across species.
  • During translation, the mRNA codon is recognized by a complementary anticodon on tRNA.
  • The anticodon sequence allows tRNA to pair with the codon in mRNA in an antiparallel orientation.
  • For example, the aminoacyl-tRNA Ile (isoleucine) has an anticodon sequence 5'-GAU-3', pairing with the isoleucine codon 5'-AUC-3'.
  • Every preprocessed eukaryotic protein starts with methionine, and the codon for methionine (AUG) is the start codon.
  • Three codons (UGA, UAA, and UAG) encode for termination of protein translation; no charged tRNA molecules recognize these codons.

Mutations

Degeneracy and Wobble
  • The genetic code is degenerate because more than one codon can specify a single amino acid.
  • All amino acids except methionine and tryptophan are encoded by multiple codons.
  • For amino acids with multiple codons, the first two bases are usually the same, and the third base varies.
  • The variable third base in the codon is called the wobble position.
  • Wobble protects against mutations in the codon region of DNA.
  • Mutations in the wobble position are often silent or degenerate, with no effect on amino acid expression.
  • For example, glycine requires only the first two nucleotides of the codon to be GG; the third nucleotide can be A, C, G, or U without changing the amino acid.
Missense and Nonsense Mutations
  • A point mutation occurs when one nucleotide in a codon is changed.
  • Expressed point mutations can affect the primary amino acid sequence of the protein.
  • Expressed point mutations are categorized as:
    • Missense mutation: where one amino acid substitutes for another.
    • Nonsense mutation: where the codon encodes for a premature stop codon (truncation mutation).
Frameshift Mutations
  • The three nucleotides of a codon are referred to as the reading frame.
  • A frameshift mutation occurs when nucleotides are added to or deleted from the mRNA sequence.
  • Insertion or deletion of nucleotides shifts the reading frame, resulting in changes in the amino acid sequence or premature truncation of the protein.
  • The effects of frameshift mutations are typically more serious than point mutations, depending on where the mutation occurs within the DNA sequence.