Molecular Biology

Wobble and Superwobble

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Science  15 Feb 2008:
Vol. 319, Issue 5865, pp. 878
DOI: 10.1126/science.319.5865.878b

In most cases, more than one triplet codon can specify an amino acid—at one extreme, leucine can be encoded by any of six nucleotide triplets. Degenerate codons tend to vary at the third position, which was the basis for Francis Crick's wobble hypothesis: Each codon must be recognized by its cognate transfer RNA (tRNA) through an anticodon that is strictly complementary at the first two positions, but can use nonstandard base-pairing in the third, or wobble, position. Applying these complementarity rules indicates that a minimum of 32 tRNAs would be needed to read all 64 possible triplet codons. Yet in human mitochondria and plant plastids, there are fewer than 32 distinct tRNAs, leading to the suggestion that tRNAs with U in their wobble position might be able to make up for the deficit by pairing with any of the four bases at the third position of the codon—via a so-called superwobble.

Plastids in tobacco plants have two tRNA genes that code for the amino acid glycine (Gly): tRNAGly(GCC), which can decode GGC and GGU Gly codons, and tRNAGly(UCC), which, according to the superwobble hypothesis, should be able to decode both its regular Gly codons, GGA and GGG, and also GGC and GGU. Rogalski et al. support this idea by individually knocking out both tRNAGly genes and showing that only the superwobble tRNA is essential for cell survival. Although tRNAGly(UCC) suffices for accurate reading of the code through superwobble, translation efficiency nonetheless seems to be reduced, explaining why superwobble is rarely selected for in genetic systems. — GR

Nat. Struct. Molec. Biol. 15, 10.1038/nsmb1370 (2008).

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