Wobble base pair



In molecular biology, a wobble base pair is a non-Watson-Crick base pairing between two nucleotides in RNA molecules. The four main wobble base pairs are guanine-uracil, inosine-uracil, inosine-adenine, and inosine-cytosine (G-U, I-U, I-A and I-C). 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.

tRNA wobble
In the genetic code, there are $$4^3$$ = 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.

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.

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:

Revised pairing rules