CHAPTER 37

• three-letter code words called codons
• the collection of these codons, once transcribed into mRNA, makes up the genetic code.
• The letters A, T, G, and C correspond to the nucleotides found in DNA
• In RNA, U (uracil) takes the place of T (thymine)
• Within the protein-coding genes, these nucleotides are organized into three-letter code words called codons, and the collection of these codons, once transcribed into mRNA, makes up the genetic code
• In eukaryotic cells, the large mRNA precursors contain coding regions (exons) will form the mature mRNA and long intervening sequences (introns) separate the exons
• The mRNA is processed within the nucleus, and the introns, which make up much more of this RNA than the exons, are removed
• Exons are spliced together to form mature mRNA, which is transported to the cytoplasm, where it is translated into protein
• The Genetic Code


  • The genetic code is a dictionary that identifies the correspondence between a sequence of nucleotide bases and a sequence of amino acids
  • Each individual word in the code is composed of three nucleotide bases
  • Each codon is consist of a sequence of three nucleotides, known as a triplet code
  • The nucleotide sequence of an mRNA molecule contains a series of codons that specify the amino acid sequence of the encoded protein
• Three of the 64 possible codons (UAA, UAG, and UGA) do not code for specific amino acids and are termed as nonsense codons
• These nonsense codons are utilized in the cell as translation termination signals where the polymerization of amino acids into a protein molecule is to stop
• Characteristics of the Genetic Code

  • Degenerate
  • Unambiguous
  • Nonoverlapping
  • Without punctuation
  • Universal
• The remaining 61 codons code for the 20 naturally occurring amino acids
• Some amino acids are encoded by several codons, i.e., 6 different codons, UCU, UCC, UCA, UCG, AGU, and AGC all specify serine
• Other amino acids, such as methionine and tryptophan, have a single codon
• The reading of the genetic code during the process of protein synthesis does not involve any overlap of codons. Thus, the genetic code is nonoverlapping
• Once the reading is commenced at a specific start codon, there is no punctuation between codons, and the message is read in a continuing sequence of nucleotide triplets until a translation stop codon is reached
• Characteristics of the Genetic Code

  • Without Punctuation: Once the reading is commenced at a specific start codon, there is no punctuation between codons, and the message is read in a continuing sequence of nucleotide triplets until a translation stop codon is reached. For example, ABCDEFGHIJKL is read as ABC DEF GHI JKL without any "punctuation" between the codons.
  • Unambiguous: The genetic code is unambiguous or specific— that is, given a specific codon, only a single amino acid is indicated. For a given codon in the mRNA, only a single species of tRNA molecule possesses the proper anticodon. With few exceptions, given a specific codon, only a specific amino acid will be incorporated— although, given a specific amino acid, more than one codon may be used.
  • Universal: The genetic code is virtually universal. The specificity of the genetic code has been conserved from very early stages of evolution, with only slight differences in the manner in which the code is translated. An exception occurs in mitochondria, where the set of tRNA molecules differs from the tRNA molecules in the cytoplasm of even the same cells.
• In the mitochondria

  The codons AGA and AGG are read as stop or chain terminator codons rather than as Arg
• As a result of organelle-specific changes in genetic code

  Mitochondria require only 22 tRNA molecules to read their genetic code, whereas the cytoplasmic translation system possesses a full complement of 31 tRNA species
• Translation is the process of translating information accurately and efficiently from the nucleotide sequence of an mRNA into the sequence of amino acids of the corresponding specific protein
• Components Required for Translation

  • Amino acids: All the amino acids that eventually appear in the finished protein must be present at the time of protein synthesis. If one amino acid is missing (for example, if the diet does not contain an essential amino acid), that amino acid is in limited supply in the cell, and translation, therefore, stops at the codon specifying that amino acid.
  • Transfer RNA (tRNA): At least one specific type of tRNA is required per amino acid. Amino acid attachment site, Anticodon, Wobble Hypothesis
• The Wobble Hypothesis describes the mechanism by which tRNAs can recognize more than one codon for a specific amino acid. It involves the base at the 5'-end of the anticodon not being as spatially defined as the other two bases, allowing nontraditional base-pairing with the 3'-base of the codon. This movement, called "wobble," allows a single tRNA to recognize more than one codon
• is not as spatially defined as the other two bases
• Movement of the first base allows nontraditional base-pairing with the 3'-base of the codon, known as "wobble", allowing a single tRNA to recognize more than one codon
• Wobbling reduces the need for 61 tRNA species to read the 61 codons coding for amino acids, requiring a total of 31 tRNAs
• Components Required for Translation

  Aminoacyl-tRNA synthetases are required for attachment of amino acids to their corresponding tRNAs. Each aminoacyl-tRNA synthetase catalyzes a two-step reaction resulting in the covalent attachment of the carboxyl group of an amino acid to the 3'-end of its corresponding tRNA. The overall reaction requires ATP, which is cleaved to AMP and Ppi
• Formation of Aminoacyl-tRNA

  A two-step reaction, involving the enzyme aminoacyl-tRNA synthetase, results in the formation of aminoacyl-tRNA. The first reaction involves the formation of an AMP-amino acid-enzyme complex. This activated amino acid is next transferred to the corresponding tRNA molecule. The AMP and enzyme are released, and the latter can be reutilized
• Specific mRNA required as a template for the synthesis of the desired polypeptide chain must be present
• Ribosomes are large complexes of protein and rRNA, consisting of two subunits - one large and one small, with relative sizes generally given in terms of their sedimentation coefficients, or S values
• Because the S values of ribosomes are determined by shape as well as molecular mass, their numeric values are not strictly additive
• The ribosome has three binding sites for tRNA molecules - the A, P, and E sites
• During translation, the A site binds an incoming aminoacyl-tRNA as directed by the codon currently occupying this site, specifying the next amino acid to be added to the growing peptide chain. The P site codon is occupied by peptidyl-tRNA carrying the chain of amino acids already synthesized. The E site is occupied by the empty tRNA as it is about to exit the ribosome
• Protein factors are required for initiation, elongation, and termination (or release) of peptide synthesis. ATP and GTP are required as sources of energy
• Three Phases of Protein Synthesis: 1. Initiation 2. Elongation 3. Termination
• Initiation of eukaryotic protein synthesis involves selecting an mRNA molecule for translation by a ribosome, locating the initiation codon, setting the correct reading frame on the mRNA, and beginning translation. This process involves tRNA, rRNA, mRNA, and at least 10 eukaryotic initiation factors (eIFs), some of which have multiple subunits. Also involved are GTP, ATP, and amino acids
• Translation

  Initiation involves tRNA, rRNA, mRNA, and at least 10 eukaryotic initiation factors (eIFs), some of which have multiple (three to eight) subunits. Also involved are GTP, ATP, and amino acids
• Translation

  Three Phases of Protein Synthesis: Initiation Involves Several Protein-RNA Complexes
• Initiation

  • The larger ribosomal subunit contains the E, P, and A site
• Translation

  Initiation codon AUG at the beginning of the message is recognized by a special initiator tRNA that enters the ribosomal P site