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Biochemistry

🧬biochemistry review

9.1 The Genetic Code and tRNA

Last Updated on August 9, 2024

The genetic code is the rulebook for translating DNA into proteins. It defines how sequences of nucleotides in mRNA correspond to specific amino acids. This system relies on codons, three-letter "words" that specify which amino acid to add next during protein synthesis.

tRNA molecules are the key players in decoding genetic information. They act as adaptor molecules, matching codons to their corresponding amino acids. The anticodon loop on tRNA base-pairs with mRNA codons, ensuring the correct amino acid is added to the growing protein chain.

Codons and the Genetic Code

Understanding Codons and Their Function

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  • Codons consist of three consecutive nucleotides in mRNA that specify a particular amino acid or signal
  • Each codon corresponds to a specific amino acid or a stop signal in protein synthesis
  • The genetic code comprises 64 possible codons, including 61 that code for amino acids and 3 stop codons
  • AUG serves as the start codon, initiating protein synthesis and coding for methionine
  • Stop codons (UAA, UAG, UGA) terminate protein synthesis by signaling the end of the coding sequence
  • Degeneracy in the genetic code allows multiple codons to specify the same amino acid, enhancing genetic stability

Genetic Code Properties and Implications

  • The genetic code is nearly universal, with few exceptions across all living organisms
  • Codons are read in a non-overlapping manner, proceeding from 5' to 3' direction on the mRNA
  • Degeneracy of the code provides redundancy, protecting against some mutations
  • Most amino acids are encoded by more than one codon, with leucine and serine having six codons each
  • The genetic code is unambiguous, meaning each codon specifies only one amino acid or stop signal
  • Wobble base pairing allows some tRNAs to recognize multiple codons, increasing translation efficiency

tRNA and Anticodons

Structure and Function of tRNA

  • Transfer RNA (tRNA) molecules serve as adaptor molecules in protein synthesis
  • tRNA structure resembles a cloverleaf when depicted in 2D, but forms an L-shape in 3D
  • The anticodon loop contains the three-nucleotide anticodon sequence complementary to mRNA codons
  • The acceptor stem of tRNA carries the amino acid corresponding to its anticodon
  • tRNAs undergo extensive post-transcriptional modifications, enhancing their stability and function
  • Specific tRNA molecules exist for each amino acid, with some amino acids having multiple tRNA variants

Anticodons and the Wobble Hypothesis

  • Anticodons are three-nucleotide sequences on tRNA that base-pair with mRNA codons
  • The wobble hypothesis, proposed by Francis Crick, explains how some tRNAs can recognize multiple codons
  • Wobble base pairing occurs at the third position of the codon, allowing non-standard base pairing
  • This phenomenon reduces the total number of tRNAs required for translation
  • Inosine, a modified base found in some tRNA anticodons, can base-pair with U, C, or A
  • Wobble pairing contributes to the degeneracy of the genetic code and translation efficiency

Protein Synthesis

Aminoacyl-tRNA Synthetases and tRNA Charging

  • Aminoacyl-tRNA synthetases catalyze the attachment of amino acids to their corresponding tRNAs
  • Each aminoacyl-tRNA synthetase specifically recognizes and charges one amino acid to its cognate tRNA
  • The charging process occurs in two steps: amino acid activation and transfer to tRNA
  • ATP is required for the activation step, forming an aminoacyl-AMP intermediate
  • Synthetases ensure the fidelity of protein synthesis by correctly pairing amino acids with tRNAs
  • Some synthetases have editing mechanisms to correct mischarging errors, maintaining translation accuracy

Codon-Anticodon Interactions in Translation

  • During translation, mRNA codons base-pair with tRNA anticodons in the ribosome
  • The ribosome moves along the mRNA in the 5' to 3' direction, reading one codon at a time
  • Codon-anticodon recognition occurs in the A site of the ribosome during the elongation phase
  • Correct base pairing between codon and anticodon triggers conformational changes in the ribosome
  • These changes promote peptide bond formation and translocation of the tRNA-mRNA complex
  • The genetic code's redundancy allows for some flexibility in codon-anticodon pairing, facilitated by wobble base pairing