THE SYNTHESIS OF PROTEINS 13 



nucleic acids for the first time presents a possible opportunity to attack 

 directly the "coding" problem. Since transfer RNA is a linear polymer 

 of four bases, it is a reasonable guess that the specificity of reaction 

 with amino acids is a function of a sequence of bases somewhere in the 

 molecule. If this is so, then it should ultimately be possible to relate 

 the base sequence to amino-acid binding, to decipher the code in 

 nucleic acid that defines each amino acid. The first step in the experi- 

 mental approach is to fractionate transfer RNA into its component 

 amino-acid-reacting species. Very encouraging progress is being made 

 in this approach ( Holley and Doctor, 1960; Zamecnik et al., 1960 ) . 

 Once the pure species are isolated, the second step will be the deg- 

 radation of the molecules to obtain base-sequence information. 



The second implication of the transfer-RNA story is that it sug- 

 gests, through the adaptor hypothesis, a reasonable chemical mecha- 

 nism by which coded fragments of RNA might be used to arrange 

 amino acids in a specific sequence in protein. The theory is being put to 

 experimental test in a number of ways. One approach is a study of the 

 species specificity in the interaction of transfer RNA and ribosomes. 

 Since transfer RNA deals directly with amino acids and is not capable 

 by itself of determining an amino-acid sequence, ribosomes of a given 

 species should be able to make their own specific proteins using trans- 

 fer RNA from any other species. Preliminary studies with ribosomes 

 from reticulocytes appear to support this prediction (Lamfrom, 1960; 

 Bishop et al, I960) . 



Another approach is to determine whether the transfer-RNA mole- 

 cules actually accompany their bound amino acids into the ribosomes 

 during the course of protein synthesis. This matter is actively under in- 

 vestigation, and it may be said that the amino-acid-bearing transfer- 

 RNA molecules do appear to pass through the ribosomes {i.e., become 

 briefly indistinguishable from ribosomal RNA ) during the course of the 

 incorporation of the amino acids into protein (Zamecnik, 1960; Hoag- 

 land and Comly, 1960). C^^-amino acids attached to transfer RNA are 

 also found transiently associated with ribosomal RNA during the incor- 

 poration process (presumably still attached to their transfer-RNA 

 adaptors). There is, furthermore, no evidence of any substantial frag- 

 mentation of transfer RNA during the course of protein synthesis. More 

 detailed kinetic analvsis of the interaction of transfer RNA and ribo- 

 somes using transfer-RNA-amino acid labeled with P'^- in its RNA 

 moiety and C^* in its amino-acid moiety suggests that substantially all 

 of the transfer-RNA molecule accompanies its attached amino acid into 

 the ribosome. The picture is thus far consistent with the adaptor 

 hypothesis. 



It should also be possible to study the nature of the chemical fink- 

 age between transfer RNA and ribosomal RNA. Is there evidence of 



