Expression of the histidine (his) operon in Salmonella typhimurium was found to be positively correlated with the intracellular level of guanosine tetraphosphate (ppGpp). Limitation for amino acids other than histidine elicited a histidineindependent metabolic regulation of the operon. In bacteria grown at decreased growth rates, his operon expression was metabolically regulated up to a point, after which further decreases in growth rate no longer resulted in further enhancement of operon expression. Studies using strains carrying various regulatory and deletion mutations indicated that metabolic regulation is achieved predominantly by increased RNA chain initiations at the primary (P1) and internal (P2) promoters. Metabolic regulation ordinarily did not involve changes in RNA chain terminations at the attenuator site of the his operon. A model is proposed that involves ppGpp-induced changes in RNA polymerase initiation specificity at particular promoters. A second, special form of metabolic regulation may operate which also is histidine independent, but does involve relief of attenuation. Expression of the histidine (his) operon inSalmonella typhimurium is exerted predominantly at the level of mRNA production (22) and appears to involve two major control sites, the primary promoter (P1) and a transcriptional barrier called the attenuator (Atn) (3,22). Thus, overall operon expression involves both the frequency of RNA chain initiations at P1 and the frequency ofpremature RNA chain terminations at Atn (Fig. 1). Data obtained from in vivo and in vitro experiments indicate that mutation hisO2355 at least in part defines the P1 site and deletion hisO1242 defines the Atn site (13,15,22).The model also hypothesizes the existence of a positive factor (46), acting to relieve the transcriptional terminations otherwise occurring at the attenuator (anti-Atn). Three mutational sites, hisO2965, hisO2966, and hisO3148, seem to affect relief of attenuation (13, 22); thus, the site of positive-factor interaction is represented by the broad bracket labeled "Anti-Atn" in Fig.

Viroids are very small, unencapsidated RNAs that replicate and induce severe disease in plants without encoding for any proteins. The mechanisms by which the viroid RNA regulates these events and interacts with host factors are unknown. An Mr 68,000 host-encoded protein has been identified that is differentially phosphorylated in extracts from viroid-infected and mock-inoculated tissues. This phosphoprotein is immunologically related to a double-stranded (ds) RNA-dependent protein kinase from virus-infected, interferon-treated human cells. Further, nucleotide photoaffinity labeling indicates that the protein has an ATP binding site. This protein is similar to dsRNA-dependent protein kinases implicated in mammalian systems in the regulation of protein synthesis and virus replication.