ROLE OF NUCLEIC ACIDS 79 



fraudulent incorporation of abnormal purines or pyrimidines, result in deep 

 changes in protein synthesis. The effects can be more or less drastic: 

 protein synthesis can be stopped or only reduced to a certain extent. Under 

 these latter conditions, different proteins can be affected to various degrees 

 and abnormal proteins can be produced. This clearly indicates that the 

 integrity of certain RNA fractions is a necessary requirement for the syn- 

 thesis of normal protein. That changes in protein structure result from 

 changes in RNA composition is probably the most convincing evidence for 

 a control of protein structure by RNA. Of all cellular RNAs, soluble 

 RNAs are the first to be affected by the destructive action of RNase and the 

 first to be deeply changed by analogues. It would seem that modification of 

 some soluble RNA fraction is enough to block or to upset the specificity 

 of the process. Evidence from the restoration of protein synthesis after 

 inhibition by ribonuclease or by azaguanine indicates, however, that 

 soluble RNA is rather easily replaced by the cell when favourable condi- 

 tions are returned. To the contrary, damage caused by the same agents, 

 most probably to another type of RNA, which also affect the specificity of 

 protein synthesis, becomes easily irreversible. 



A thorough study of changes brought about in protein structure by 

 modifications of RNA may afford a means of studying the most puzzling 

 aspect of protein synthesis, namely the control of specificity. 



Beside the agents mentioned above — purine and pyrimidine analogues 

 and ribonuclease — the use of nitrous acid for the limited deamination of 

 nucleic acid adenine, guanine and cytosine might prove very informative 

 in this respect. Hexetidine has also been shown to alter the specificity of 

 protein synthesis in a bacterium (Halvorson and Gorman, 1959). 



Chloromycetine strongly inhibits protein synthesis in bacteria. The 

 action of this antibiotic closely resembles the effects of azaguanine in many 

 respects; it probably acts at about the same point upon the mechanism 

 of protein synthesis. Closer analysis of the various substances which dis- 

 sociate protein and RNA synthesis in different ways (Gale and Folkes, 

 1953 ; Gale, 1958) remains certainly one of the promising approaches to the 

 understanding of the exact function of RNA. 



4. RNA as the Genetic Messenger 



At the end of Chapter II, it was concluded that DNA is not directly 

 involved in the synthesis of most proteins, and that the genetic informa- 

 tion it contains must be transferred to some other substance before serving 

 in the synthesis of cytoplasmic proteins. 



The common belief is at present that the substance which carries the 

 genetic information from DNA to cytoplasmic centres of protein synthesis 

 must be a RNA. This is one side of what Crick (1958) called the 'central 

 dogma', thus making it clear that this opinion rests largely on a priori 



