Wobble base pair
In molecular biology, the Central Dogma, as proposed by Francis Crick, follows the pathway from DNA to RNA and finally to a polypeptide sequence. A transcribed DNA template is changed to an mRNA and that is copied into an amino acid sequence through tRNA's matching to the correct codons. These codons on the mRNA line up with anticodons on the tRNA. A wobble base pair is a pairing between two nucleotides in RNA molecules, that does not follow Watson-Crick base pair rules.  The four main wobble base pairs are guanine-uracil (G-U), hypoxanthine-uracil (I-U), hypoxanthine-adenine (I-A), and hypoxanthine-cytosine (I-C). Because hypoxanthine is the nucleobase of inosine, "I" is used for the former in order to maintain consistency of nucleic acid nomenclature, which otherwise follows the names of the nucleobases (e.g., "G" for both guanine and guanosine). The thermodynamic stability of a wobble base pair is comparable to that of a Watson-Crick base pair. Wobble base pairs are fundamental in RNA secondary structure and are critical for the proper translation of the genetic code.
In the genetic code, there are = 64 possible codons (tri-nucleotide sequences). For translation, each of these codons requires a tRNA molecule with a complementary anticodon. If each tRNA molecule paired with its complementary mRNA codon using canonical Watson-Crick base pairing, then 64 types (species) of tRNA molecule would be required. In the standard genetic code, three of these 64 codons are stop codons, which terminate translation by binding to release factors rather than tRNA molecules, so canonical pairing would require 61 species of tRNA. Since most organisms have fewer than 45 species of tRNA, some tRNA species must pair with more than one codon. In 1966, Francis Crick proposed the Wobble hypothesis to account for this. He postulated that the 5' base on the anticodon, which binds to the 3' base on the mRNA, was not as spatially confined as the other two bases, and could, thus, have non-standard base pairing. Crick creatively named it for the small amount of play that occurs at this third codon position. Movement ("wobble") of the base in the 5' anticodon position is necessary for small conformational adjustments that affect the overall pairing geometry of anticodons of tRNA .
As an example, yeast tRNAPhe has the anticodon 5'-GmAA-3' and can recognize the codons 5'-UUC-3' and 5'-UUU-3'. It is, therefore, possible for non-Watson–Crick base pairing to occur at the third codon position, i.e., the 3' nucleotide of the mRNA codon and the 5' nucleotide of the tRNA anticodon.
These notions led Francis Crick to the creation of the wobble hypothesis, a set of four relationships explaining these naturally occurring attributes. 1. The first two bases in the codon create the coding specificity, for they form strong Watson-Crick base pairs and bond strongly to the anticodon of the tRNA. 2. When reading 5' to 3' the first nucleotide in the anticodon (which is on the tRNA and codes with the last nucleotide of the codon on the mRNA) determines how many nucleotides the tRNA actually distinguishes. If the first nucleotide in the anticodon is a C or an A pairing is specific and acknowledges original Watson-Crick pairing, that is only one specific codon can be paired to that tRNA. If the first nucleotide is U or G, the pairing is less specific and in fact two bases can be interchangeably recognized by the tRNA. Inosine displays the true qualities of wobble, in that if that is the first nucleotide in the anticodon then any of three bases in the original codon can be matched with the tRNA. 3. Due to the specificity inherent in the first two nucleotides of the codon, if one amino acid codes for multiple anticodons and those anticodons differ in either the second or third position (first or second position in the codon) then a different tRNA is required for that anticodon. 4. The minimum requirement to satisfy all possible codons(61 excluding three stop codons) is 32 tRNAS. That is 31 tRNA's for the amino acids and one initiation codon.
tRNA base pairing schemes
The original wobble pairing rules, as proposed by Crick. Watson-Crick base pairs are shown in bold, wobble base pairs in italic:
|tRNA 5' anticodon base||mRNA 3' codon base|
|G||C or U|
|U||A or G|
|I||A or C or U|
Revised pairing rules
|tRNA 5' anticodon base||mRNA 3' codon base|
|I||A or C or U|
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- tRNA, the Adaptor Hypothesis and the Wobble Hypothesis
- Wobble base-pairing between codons and anticodons
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