In translation of the genetic information present in the messenger RNA using transfer RNA during protein biosynthesis, Crick suggested, in 1966, that base pairing of the first (5′ ) base of the anticodon of transfer RNA with that at the third (3′ ) position of the codon (see Genetic Code) does not necessarily conform to normal Watson-Crick base pairing (1). He introduced the term wobble pairing for this noncanonical base pairing. Crick pointed out, as a typical example of wobble pairing, that the inosine (I) (a derivative of G) located at the first position of the yeast tRNAAla anticodon can base-pair at the third position of the codon with not only C but also with U and A. Since then, as nucleotide sequences of numerous tRNAs from various sources have been determined (2), knowledge of the extent of wobble pairing has expanded, as shown in Table 1. (See top of next page) The wobble pairings have been verified experimentally both in vitro (3) and in vivo (4).
Table 1. Anticodon-Codon Paring Rules So Far Elucidated2
|
5′ |
3′ Occurrence |
|
Anticodon |
Codon5′ |
|
1. U or modified U at the wobble positionof the anticodon |
|
|
a. Unmodified U |
|
|
UNN UNN |
UNN UNN Family boxes in mitochondria, |
|
Mycoplasma spp., and chloroplasts |
|
|
AN’N’ UN’N’ |
CN’N’ GN’N’ |
|
b. U modified to U* |
(mo5U or cmo5U) |
|
U*NN U*NN |
U*NN Family boxes in eubacteria |
|
AN’N’ UN’N’ |
GN’N’ |
|
c. U modified to U+ |
(Um, cmnm5U, or mcm5U) |
|
U+NN U+NN |
2-codon sets in mitochondria, bacteria |
|
and eukaryotes |
|
|
AN’N’ GN’N’ |
|
|
d. U modified to U# |
(mnm s U, mcnm s U or cmnm s U) |
|
U#NN U#NN |
2-codon sets in eubacteria and eukaryotes |
|
AN’N’ GN’N’ |
|
|
2. G or modified G at the wobble positionof the anticodon |
|
|
a. Case 1 for unmodified G |
|
|
GNN GNN |
2-codon sets of all organisms, and family |
|
|
boxesin bacteria |
||
|
CN’N’ UN’N’ |
||
|
b. Case 2 for unmodified G |
||
|
GNN GNN |
GNN |
IleAUN (except AUG) and AsnAAN |
|
(except AAG) instarfish mitochondria. |
||
|
SerAGN (except AGG) in Drosophila |
||
|
CN’N’ UN’N’ |
AN’N’ |
mitochondria |
|
c. G modified to Q |
||
|
QNN QNN |
2-codon sets in eubacteria and eukaryotes |
|
|
CN’N’ UN’N’ |
||
|
d. G modified to I |
||
|
INN INN |
INN |
ArgCGN in eubacteria, and all family |
|
boxes ineukaryotes except GlyGGN |
||
|
CN’N’ UN’N’ |
AN’N’ |
|
|
e. G modified to G* (m7G) |
||
|
G*NN G*NN |
G*NN G*NN SerAGN in starfish and squid |
|
|
mitochondria |
||
|
CN’N’ UN’N’ |
AN’N’ GN’N’ |
|
|
3. A at the wobble position of the anticodon(rare) |
||
|
ANN ANN |
ANN ANN |
ThrACU and ArgCGN in mycoplasma |
|
spp. and yeastmitochondria. ArgCGN in |
||
|
UN’N’ CN’N’ |
GN’N’ AN’N’ |
nematode mitochondria |
|
4. C or modified C at the wobble positionof the anticodon |
||
|
a. Unmodified C |
||
|
CNN |
5′ 3′ Only N N G codons in all organisms |
|
|
GN N |
||
|
b. C modified to C*(f5C) |
||
|
C*AU C*AU |
MetAUR in animal mitochondria |
|
|
GUA AUA |
||
|
c. C modified to L |
||
|
LAU |
IleAUA in eubacteria and plant |
|
|
mitochondria |
||
|
AUA |
||
a The anticodon-codon pairing is shown by 5 ‘ANTICODON (NNN)3‘ 3‘CODON(N’N ‘N’)5 ‘ where N in the anticodon and its corresponding N in the codon (beneath the N) form Watson-Crick base pairing. The underlined letters are involved in wobble pairing. Family box means that 4 synonymous codons are included in a box in the genetic code table (for example, GUU, GUC, GUA and GUG for Val codons). 2-codon set means that only 2 codons are used for one amino acid (for example, AAA and AAG for Lys codons).
Abbreviations used are: mo5U, 5-methoxy U; cmo5U, 5-carboxymethoxy U; cmnm 5U, 5-carboxymethyl-aminomethyl U; mcm5U, 5-methylcarboxymethyl U; Um, 2 ‘-O-methyl U; mnms U, 5-methylaminomethyl-2-thio U, cmnmrU, 5-carboxymethyl-aminomethyl-2-thio U; mcmrU, 5-methylcarboxymethyl-2-thio U; Q, queosine (in eubacteria) or its derivatives, manQ or galQ (in eukaryotes); f 5C, 5-formyl C; L, lysidine. From Osawa (5) with modifications (6, 7). See also Bjork (8).
The importance of wobble is that there is no need for a unique transfer RNA specific for each codon of the genetic code. Consequently, one transfer RNA can respond to several codons, inserting the same amino acid for each.
