Review Question - QID 108474

The wobble hypothesis is that accurate tRNA base pairing often requires only the first two nucleotides to be recognized. Differences in the third "wobble" position often results in the same amino acid due to degeneracy in the genetic code.

This scenario tests basic scientific concepts with regards to protein translation and the central dogma. The process begins with recognition of the Kozak consensus sequence in an mRNA and subsequent assembly of the ribosome. An initatior methionine is then set in the P position of the ribosome. Elongation is the next step and involves binding of specific tRNA anticodon loops to the codons of the mRNA. The specificity of this process is ensured by charging tRNA with the correct amino acid, and then having these tRNA recognize the correct codon. There are 64 codons (4x4x4) and only 20 amino acids so many codons code for the same amino acids, a feature known as codon degeneracy. This occurs because some tRNAs require only the first two nucleotides of a codon to be recognized and accept any nucleotide at the third position. Therefore, the mutation of every third nucleotide had no effect on the amino acid sequence encoded. This process is known as the wobble hypothesis.

Incorrect Answers:
Answer 1: Covalent alterations occur to both nucleotides (such as isomerization in tRNAs) and proteins (such as post-translational carboxylation and glycosylation). These may affect the fucntion of proteins and structural RNA but does not lead to codon changes in mRNA.

Answer 2: mRNA splicing is a process by which only some of the DNA sequences initially transcribed into pre-mRNA are present in the final mRNA. The intervening sequences are removed by spliceosome machinery prior to mRNA exit from the nucleus.

Answer 3: Translational proofreading is the process by which ribosomes check the correct pairing between the mRNA codon and the tRNA anticodon. It involves requiring a GTPase to hydrolyse its GTP faster than the tRNA dissociates. This process corrects abnormal pairing but does not affect normal codon structure.

Answer 4: Trimming of specific amino acids activates some proteins after translation and is primarily used when these proteins need to be activated in a regulated manner. One example is processing of trypsinogen into trypsin by enteropeptidase.

Bullet Summary:
Codon degeneracy means that several different codons are translated to the same amino acid. One major mechanism by which this happens is the "wobble hypothesis" which states that some tRNAs only require accurate pairing of the first two nucleotides and are permissive at the third position.