Schindler D, Echols H
Proc Natl Acad Sci U S A. 1981 Jul;78(7):4475-9. doi: 10.1073/pnas.78.7.4475.
Bacteriophage lambda regulates the integration--excision reaction as a crucial aspect of the choice of pathway during lysogenic or lytic viral development. This control involves differential expression of the tightly linked, partially overlapping int and xis genes from two promoter sites: pI, positively regulated by cII/cIII proteins, and pL, positively regulated by N protein. After lambda infection, Int is synthesized from the pI transcript under cII regulation; however, very little Int is produced from the pL RNA because of the existence of a cis-acting regulatory element, sib, on the opposite side of the int gene from the pL promoter. Presumably sib serves to prevent unwanted synthesis of Int protein during the lytic response; the Int protein necessary for excisive recombination from a prophage can be supplied by pL transcription because sib is separated from int by prophage insertion. We have studied the effect of sib on nearby lambda genes by means of gel electrophoresis of labeled proteins from infected cells. Deletion of the sib region greatly enhances production of Int protein without substantial effect on Xis production; thus, sib regulation normally is highly specific for Int. When the sib region is moved past int and xis by deletion, regulation of the adjacent gene for the protein Ea22 occurs, suggesting that sib regulation can work on other genes. Although synthesis of wild-type Int is severely inhibited by sib, shorter Int protein fragments generated by nonsense mutations escape sib regulation, indicating that the regulation is translational and occurs near the completion stage of protein synthesis. Regulation by sib thus exhibits novel regulatory features: distal location, recombinational control, and regulation of the completion of protein synthesis. Because Int and Ea22 control is lost in a RNase III- host, we suggest that sib regulation might involve RNase III cleavage of a RNA duplex region that includes sib and the regulatory target (normally the int gene). We note such a potential site within int.
噬菌体λ调控整合-切除反应，这是溶原性或裂解性病毒发育过程中途径选择的关键方面。这种调控涉及从两个启动子位点对紧密连锁、部分重叠的int和xis基因进行差异表达：pI受cII/cIII蛋白正向调控，pL受N蛋白正向调控。λ感染后，Int在cII调控下从pI转录本合成；然而，由于int基因与pL启动子相对侧存在顺式作用调控元件sib，从pL RNA产生的Int很少。推测sib用于防止裂解反应期间Int蛋白的不必要合成；来自原噬菌体的切除重组所需的Int蛋白可由pL转录提供，因为sib通过原噬菌体插入与int分开。我们通过对感染细胞中标记蛋白进行凝胶电泳，研究了sib对附近λ基因的影响。删除sib区域可大大增强Int蛋白的产生，而对Xis的产生没有实质性影响；因此，sib调控通常对Int具有高度特异性。当sib区域通过缺失移过int和xis时，会发生对Ea22蛋白相邻基因的调控，这表明sib调控可作用于其他基因。尽管野生型Int的合成受到sib的严重抑制，但由无义突变产生的较短Int蛋白片段可逃避sib调控，这表明该调控是翻译水平的，且发生在蛋白质合成的完成阶段附近。因此，sib调控具有新颖的调控特征：远端定位、重组控制和对蛋白质合成完成的调控。由于在RNase III -宿主中失去了对Int和Ea22的控制，我们认为sib调控可能涉及对包含sib和调控靶标（通常是int基因）的RNA双链区域进行RNase III切割。我们在int内注意到这样一个潜在位点。
