VIII. PROTEIN SYNTHESIS AND GENE ACTION 397 



of the autoradiographic studies, it is likely that the synthesis involved 

 ribosomal RNA, based on the large amount of synthesis. The finding of 

 a rapidly labeled RNA with the base composition of DNA (Sibatani 

 et al., 1962) in thymus nuclei is evidence that "informational" RNA 

 can be synthesized in the nucleus. The demonstration of an RNA poly- 

 merase enzyme in thymus nuclei (Weiss, 1960) is consistent with this 

 viewpoint. The association of newly synthesized RNA with chromatin 

 DNA (Bonner et al., 1961) using pea embryo preparations is also sug- 

 gestive of this type of RNA, which may also be a precursor of ribosomal 

 RNA. However, it is not yet known whether messenger RNA synthesis 

 occurs exclusively in the nucleus, or also to a small extent in the cyto- 

 plasm. In addition, is there destruction of messenger RNA and replace- 

 ment into old ribosomes from nuclear messenger RNA as in bacteria? 

 Or is the complete package made in the nucleus? The continued synthesis 

 of protein in the absence of a nucleus and of net RNA synthesis (see 

 Goldstein et al., 1960, for references!, does not exclude the presence of 

 a small fraction of RNA with a rapid turnover, presumably synthesized 

 under the direction of cytoplasmic DNA. The alternative is a stable 

 messenger RNA integrated into the ribosome. During the lifetime of a 

 nucleated cell, depending on the stage of differentiation, it is possible 

 that both mechanisms play a role. 



The messenger RNA hypothesis (Jacob and ]Monod, 1961) is based 

 on phenomena observed in bacteria, and we have seen that, though no 

 rigorous proof is available, the circumstantial evidence is largely con- 

 sistent with it. Rapid adaptation is a characteristic, and indeed neces- 

 sary, property of bacteria. On the other hand, although adaptation is not 

 unknown in cells of higher organisms, the changes which normally occur 

 are slow and often irreversible. Thus, information turnover might differ 

 in rate and even in basic mechanism from that in bacteria. 



3. Studies with Cell-Free Systeins 



Studies of information transfer with cell-free systems of higher 

 organisms have been done mainly with the reticulocyte sj^stem. This 

 type of cell represents an extreme degree of differentiation. Measure- 

 ments of P^- and guanosine incorporation into RNA of intact reticulo- 

 cytes showed a turnover of RNA too low to be compatible with 

 messenger RNA fonnation during hemoglobin synthesis (Nathans et al., 

 1962). Similar results were obtained in this laboratorJ^ For example, 

 after 2 hours of incubation of intact reticulocytes, the incorporation of 

 either P^-- or H^-cytidine into total RNA was between 0.1 to 0.5 

 m/xmoles per ml of packed cells, while amino acid incorporation was 

 6.000 to 10.000 m/^moles. (O. Favelukes and R. Schweet, unpublished 



