Carter-Muenchau P, Wolf R E
Department of Biological Sciences, University of Maryland, Baltimore County 21228.
Proc Natl Acad Sci U S A. 1989 Feb;86(4):1138-42. doi: 10.1073/pnas.86.4.1138.
Previous work has shown that in Escherichia coli K-12 growth-rate-dependent regulation of expression of 6-phosphogluconate dehydrogenase, encoded by the gnd gene, occurs at the posttranscriptional level and is mediated by a negative control element that lies deep in the coding sequence, somewhere between codons 48 and 118. Deletion analysis of a growth-rate-regulated gnd-lacZ translational fusion showed that the element is the segment of gnd mRNA between codons 67 and 78 that is complementary to an extensive portion of the gnd ribosome-binding site, including its Shine-Dalgarno sequence. The boundaries of the element were further defined by the cloning of a synthetic "internal complementary sequence." The core internal complementary sequence element effected growth-rate-dependent regulation when placed at several sites between codon 40 and codon 69, but it severely reduced gene expression when moved to codon 13. The effect on regulation of single and double mutations introduced into the element by site-directed mutagenesis correlated with the ability of the respective mRNAs to fold into secondary structures that sequester the ribosome-binding site. Thus the gnd gene's internal regulatory element appears to function as a cis-acting antisense RNA.
先前的研究表明,在大肠杆菌K-12中,由gnd基因编码的6-磷酸葡萄糖酸脱氢酶的表达受生长速率依赖性调控,该调控发生在转录后水平,由位于编码序列深处、密码子48至118之间的一个负调控元件介导。对一个受生长速率调控的gnd-lacZ翻译融合体进行缺失分析表明,该元件是gnd mRNA中密码子67至78之间的片段,它与gnd核糖体结合位点的大部分区域互补,包括其Shine-Dalgarno序列。通过克隆一个合成的“内部互补序列”进一步确定了该元件的边界。当核心内部互补序列元件置于密码子40至69之间的几个位点时,可实现生长速率依赖性调控,但移至密码子13时则会严重降低基因表达。通过定点诱变引入该元件的单突变和双突变对调控的影响与各自mRNA折叠成隔离核糖体结合位点的二级结构的能力相关。因此,gnd基因的内部调控元件似乎起着顺式作用反义RNA的功能。