406 MAHLON B. HOAGLAND 



is simply "junk" RNA used to carry the coding end. Such RNA would, 

 thus, not itself be required to have specific genetic structure and hence 

 might be synthesized by nonspecific means from any available nucleotides. 



A second problem in respect to the adaptor hypothesis is less easy to 

 answer experimentally at this juncture. How does the hypothesis envision 

 the arrangement of template RNA and adaptors such that amino acids 

 would be brought into the proper contiguity for condensation with their 

 neighbors? This question is mentioned only to emphasize the importance of 

 learning more about the actual physical state of the RNA in the particles. 

 Presumably a variety of methods could be used by nature to make the 

 necessary spatial arrangements. Man has thus far tried few models and 

 this will become possible as our knowledge of particle structure grows. The 

 common pCpCpA end may also have some significance in the arrangement 

 in giving the amino acid the proper "reach" to join its neighbor, as has 

 been suggested by S. Brenner. 



Is the adaptor hypothesis adequate to explain the known discriminatory 

 precision of the protein synthetic process; can it, for example, account for 

 the precision with which the system rejects the wrong amino acids? If an 

 amino acid analog can be activated and attached to transfer RNA, it would 

 be expected to become incorporated into protein because the hypothesis 

 makes no provision for a further exclusion step after attachment to the 

 RNA. 



It has been shown by Sharon and Lipmann 234 that certain amino acid 

 analogs are activated by amino acid activating enzymes and that in gen- 

 eral those which can ultimately be incorporated into protein are found to 

 be the more readily activated. Loftfield and his associates 235236 have ex- 

 amined this question more critically and have concluded that the exclusion 

 of an analog from protein cannot entirely be explained by the discrimina- 

 tion of the activation step plus the attachment to transfer RNA. This is 

 based on the finding that alloisoleucine competes with valine and isoleu- 

 cine for sites on the corresponding activating enzymes and to a lesser extent 

 for sites on transfer RNA. The analog is utilized for the over-all process of 

 protein synthesis only ^2000 as well as the natural amino acids, however. 

 This question will require further critical examination, particularly under 

 conditions which simulate as closely as possible the in vivo situation. 



However, the occurrence of reactions between RNA and amino acids for 

 the first time permits a direct experimental attack on the coding problem. 

 It is of fundamental importance to determine the minimal structural re- 



234 N. Sharon and F. Lipmann, Arch. Biochem. Biophys. 69, 219 (1957). 



235 R. B. Loftfield, Proc. 4th Intern. Congr. Biochem., Vienna, 1958 Symposium 8 

 (1958). 



23 « R. B. Loftfield, L. I. Hecht, and E. A. Eigner, Federation Proc. 18, 1090 (1959). 



