Johnston H M, Barnes W M, Chumley F G, Bossi L, Roth J R
Proc Natl Acad Sci U S A. 1980 Jan;77(1):508-12. doi: 10.1073/pnas.77.1.508.
A model is proposed that accounts for regulation of the histidine operon by a mechanism involving alternative configuration of mRNA secondary structure (the alternative stem model). New evidence for the model includes sequence data on three regulatory mutations. The first (hisO1242) is a mutation that deletes sequences needed to form the attenuator mRNA stem and causes constitutive operon expression. The second mutation (hisO9654) is a His- ochre (UAA) mutation in the leader peptide gene; the existence of this mutation constitutes evidence that the leader peptide gene is translated. The third mutation (hisO9663) is remarkable. It neither generates a nonsense codon nor affects a translated sequence; yet, it is suppressible by amber suppressors. We believe this mutation causes a His- phenotype by interfering with mRNA secondary structure. The suppressibility of the mutation is probably due to disruption of the attenuator stem by ribosomes that read through the terminator codon of the leader peptide gene. This explanation is supported by the observation of derepression of a wild-type control region in the presence of an amber suppressor. Evidence is presented that hisT mutants (which lack pseudouridine in the anticodon arm of histidine tRNA) may cause derepression of the his operon by slowing protein synthesis in the leader peptide gene.
提出了一种模型，该模型通过涉及mRNA二级结构的交替构象的机制（交替茎模型）来解释组氨酸操纵子的调控。该模型的新证据包括三个调控突变的序列数据。第一个（hisO1242）是一个删除形成弱化子mRNA茎所需序列的突变，导致操纵子组成型表达。第二个突变（hisO9654）是前导肽基因中的一个组氨酸赭石（UAA）突变；该突变的存在构成了前导肽基因被翻译的证据。第三个突变（hisO9663）很显著。它既不产生无义密码子也不影响被翻译的序列；然而，它可被琥珀抑制子抑制。我们认为这个突变通过干扰mRNA二级结构导致组氨酸表型。该突变的可抑制性可能是由于核糖体通读前导肽基因的终止密码子而破坏了弱化子茎。在存在琥珀抑制子的情况下野生型控制区的去阻遏现象的观察支持了这一解释。有证据表明，hisT突变体（在组氨酸tRNA的反密码子臂中缺乏假尿苷）可能通过减缓前导肽基因中的蛋白质合成而导致组氨酸操纵子的去阻遏。
