12 MOLECULES, VIRUSES, AND BACTERIA 



the amino acid being attached to the end adenyHc acid. This grouping 

 seems to be common to all of the transfer-RNA species, and therefore 

 the specificity of amino-acid attachment must be governed by features 

 of the molecules other than the common terminal grouping. 



Transfer RNA, when charged with amino acids labeled with car- 

 bon 14, will serve as a source of these amino acids in ribosomal protein 

 under appropriate experimental conditions. This reaction requires, be- 

 sides ribosomes and transfer-RNA amino acid, GTP and soluble en- 

 zyme(s). (The role of GTP is still completely unknown.) Thus trans- 

 fer RNA fulfills certain criteria for an intermediate in protein synthesis. 

 This role is further supported by in vivo studies which show that 

 transfer RNA becomes labeled with carbon 14-amino acids earlier than 

 other cellular RNA or protein fractions (Hoagland et al., 1958; Lacks 

 and Gros, 1959); that this order of events is reversed when previously 

 labeled cells are exposed to the unlabeled analogue of the labeled 

 amino acid ( Zamecnik, 1960 ) ; that the rate of labeling of transfer RNA 

 is determined by the rate of protein synthesis, i.e., the more rapidly 

 amino acids are removed from transfer RNA by protein synthesis, the 

 more rapidly new amino acids can attach to transfer RNA ( Lacks and 

 Gros, 1959). 



None of these experiments, taken individually or as a whole, 

 proves that transfer RNA is an obligatory intermediate in protein 

 synthesis. However, the evidence is impressive enough to tempt one to 

 think that such may be the case, and a working hypothesis has been 

 oflFered to account for this finding ( Crick, 1958; Hoagland et al., 1959 ) . 

 The "adaptor" hypothesis states that amino acids, before entering the 

 ribosomes, first react chemically with specific small polynucleotide 

 molecules. These adaptor molecules accompany the amino acids into 

 the particles and are responsible for properly locating them on the 

 particle RNA. This is accomplished by pairing of the adaptor bases 

 with complementary base sequences on the particle RNA. Having ac- 

 complished their mission, tlie adaptors then return to the soluble 

 milieu. This hypothesis accounts for the specific attachment of amino 

 acids to individual RNA molecules. It accounts for the fact that these 

 events precede the appearance of amino acids in protein. It accounts 

 for the ability of transfer RNA to serve as a source of amino acids in 

 newly formed protein. 



Most important, it o£Fers a chemically attractive explanation for 

 the precision of protein synthesis: the accuracy with which the amino- 

 acid sequence is determined. For it makes the highly specific inter- 

 action of base pairs in nucleic acid responsible for locating the amino 

 acid. 



Two important implications of the transfer-RNA story need empha- 

 sis. The first is that the specific chemical interaction of amino acids and 



