IV RNA AND GROWTH PROTEIN SYNTHESIS 277 



multiplication has been obtained from an entirely different type of experiment : 

 substances which interfere with RNA metabolism (for instance thiouracil which 

 may be regarded as a competitive analogue of uracil) inhibit the synthesis of the 

 virus (Commoner and Mercer, 1951). However, an analysis of the phenomenon by 

 Jeener and Rosseels (1953) disclosed a remarkable fact: thiouracil does not act as a 

 competitive inhibitor, but it is incorporated into the virus RNA. The result is the syn- 

 thesis of an abnormal RNA and a decrease in infectivity. Identical results have been 

 obtained by Matthews (1954, 1955) with 8-azaguanine: here again, the abnormal 

 base is incorporated in the virus RNA, with a simultaneous loss of infective power. 



The obvious conclusion is that removal of the virus RNA or alteration of its 

 composition by introduction of abnormal bases always leads to an inhibition of 

 virus multiplication, i.e. to the suppression of growth. The very recent and spectacu- 

 lar experiments of Fraenkel-Conrat and Williams (1955) confirm this statement 

 in a more direct way : by proper treatment of tobacco mosaic virus, Fraenkel- 

 Conrat and Williams (1955) have succeeded in separating the protein and the 

 RNA moieties and found that neither of them are infectious. But if the two frac- 

 tions are mixed together, partial resynthesis of the virus occurs and infectivity is 

 restored to a certain extent. There is no longer any doubt that integrity of both 

 RNA and protein, and their proper combination are essential for full virus activity. 



A last and very interesting point should be discussed about the plant viruses: 

 as we already know, they show genetic continuity, i.e. they are reproduced by the 

 infected cell without any change in their specific molecular structure. We have 

 seen earlier in this chapter that DNA plays the leading part in phage genetics: 

 does RNA play a similar role in plant viruses? The question has been raised 

 recently by Jeener (1956) in a very thoughtful paper, in which he reports experi- 

 ments showing that, in infected leaves, the incorporation of radioactive CO2 is 

 higher in the non-virulent antigenic protein (soluble antigens) than in the virus; 

 it is lowest in the normal protein of the leaves. The experimental data are compati- 

 ble with the hypothesis that the soluble antigens are precursors of the virus. This 

 hypothesis is supported by the additional finding that soluble antigens accumulate 

 in the leaf as soon as the synthesis of the virus is complete. 



Jeener (1956) draws the conclusion that RNA and proteins are synthesized 

 independently in the virus-infected cell: just as in the phage, multiplication of the 

 virus is not due to the division of preexisting particles. If so, RNA could play the 

 same role in plant viruses as DNA in phage and it might represent a genetical 

 model for protein synthesis'. 



(c) Direct evidence for a role of RXA in growth and protein synthesis 



The evidence which has been reviewed so far lends strong support to the idea 



that RNA is directly concerned in growth and protein synthesis: however, the 



evidence has so far been only circumstantial. 



The first successful attempt to show that nucleic acids are directly involved in 



protein synthesis has been made by Gale and Folkes (1954, 1955a), who studied 



^ This conclusion has now been confirmed by Gierer and Schramm's (1956) important 

 finding that pure tobacco mosaic virus RNA is infective. 



Lilfralure p. zgg 



