Vlll. PROTEIN SYNTHESIS AND GENE ACTION 377 



not possible for steric reasons. As shown in Fig. IC, if growth of the 

 chain started at the C-temiinus, a similar situation would arise. How- 

 ever, if the N-teniiinal amino acid is attached first by its carboxyl 

 group and initiates chain growth (Fig. ID), the growing tip of the chain 

 (aag) is attached and can form a peptide bond with aa4, since both are 

 attached to the ribosome. The new growing tip at aa4 is still attached 

 and when aag attaches, further chain growth can continue. 



How is an ordered synthesis from the N-terminus arranged for? 

 Presumably, this is a function of the "code" and is accomplished by the 

 mechanism of interaction between messenger RNA (see Section IV) and 

 amino acid-specific transfer RNA. The first requirement for the code 

 in this viewpoint is that it can be transcribed only from a single starting 

 point, corresponding to the N-temiinal amino acid. Genetic evidence for 

 such a code has been reported by Crick et al. (1961). The mechanism by 

 which the N-terminal amino acid is positioned on the messenger RNA- 

 ribosome template first is not known, but several possibilities have been 

 discussed by Goldstein (1962). What is the mechanism by wiiich the code 

 ensures that peptides are not formed anywhere along the chain, but only 

 sequentially from the N-teiTiiinus? A simple mechanism for providing 

 this arises from a consideration of the mechanism of interaction between 

 the messenger RNA in the ribosome and the incoming amino acyl-RNA. 

 To find its proper place in the amino acid sequence, a triplet of bases in 

 the T-RNA is supposed to hydrogen bond to a triplet of bases in the 

 messenger RNA (see preceding discussion). This alone, however, is 

 postulated to be too weak an interaction to permit the amino acid to 

 remain on the template long enough to participate in further reactions. 

 If it is assumed that in addition to bonding to the code sequence of the 

 messenger RNA, the T-RNA of the incoming amino acid must bond to 

 the preceding molecule of T-RNA, then sequential growth is provided 

 for. According to this idea each T-RNA molecule, in addition to its 

 unique coding triplet of bases, must contain two common sets of 

 sequences which are complementary. For example, each T-RNA would 

 have possibly an AG-rich region and a UC-rich region at different 

 parts of the chain. AC-rich and GU-rich would work also. The AG-rich 

 and UC-rich regions might be 10 or more nucleotides in length and 

 might or might not be exactly complementary in sequence for the 

 required interactions to take place. According to this hypothesis, the 

 incoming amino acyl-RNA would have to bond both by its triplet code 

 to the messenger RNA and by its UC-rich region to the AG-rich region 

 of the T-RNA on the preceding amino acid for effective amino acid 

 transfer. Tliis would be the one at the growing tip of the chain according 

 to the previous discussion. 



