In bacteria, RNase III cleaves the initial long primary ribosomal RNA transcripts/precursors (pre-rRNAs), thereby releasing the pre-16S and pre-23S rRNAs for maturation. This cleavage is specified by the double-stranded secondary structures flanking the mature rRNAs, and not necessarily by the nucleotide sequences. Inhibition of this cleavage would lead to a build-up of pre-rRNA molecules. Doxycycline has earlier been shown to bind synthetic double-stranded RNAs and inhibit their cleavage by RNase III. Since bacterial rRNA processing is primarily dependent on RNase III cleavage (which is inhibited by doxycycline), doxycycline could therefore inhibit the normal processing of bacterial rRNA. In this study, the effect of doxycycline on bacterial rRNA processing was investigated by analyzing the amounts of various rRNAs in growing Escherichia coli cells treated with doxycycline. The results showed a doxycycline dose-dependent decrease in mature 16S and 23S rRNAs, concurrent with an accumulation of the initial rRNA transcripts and long precursors. Morphologically, treated cells were elongated at low drug concentrations, while nucleoid degeneration indicative of cell death occurred at higher drug concentrations. These observations suggest that doxycycline inhibits the cleavage and processing of bacterial rRNA transcripts/precursors, leading to impaired formation of mature rRNAs, and the consequent inhibition of protein synthesis for which the tetracycline group of antibiotics are renowned. Since rRNA structure and processing pathway is conserved among bacterial species, this mechanism may account for the broad spectrum of antibiotic activity and selective microbial protein synthesis inhibition of doxycycline and the tetracyclines.

在细菌中，RNase III裂解最初的长核糖体RNA原始转录物/前体（pre-rRNA），从而释放出16S和23S之前的rRNA使其成熟。这种切割是由成熟rRNA侧翼的双链二级结构指定的，不一定由核苷酸序列指定。抑制这种切割会导致前rRNA分子的积累。早期已证明多西环素结合合成的双链RNA，并抑制其被RNase III切割。由于细菌rRNA的加工主要取决于RNase III的裂解（被强力霉素抑制），因此强力霉素可以抑制细菌rRNA的正常加工。在这项研究中，通过分析生长过程中各种rRNA的量，研究了强力霉素对细菌rRNA加工的影响。大肠杆菌强力霉素处理的细胞。结果显示，成熟的16S和23S rRNA中强力霉素的剂量依赖性降低，同时初始rRNA转录本和长前体的积累。从形态上讲，低浓度药物可使处理后的细胞伸长，而较高浓度药物则表明细胞死亡的核苷变性发生。这些观察结果表明，强力霉素抑制细菌rRNA转录物/前体的裂解和加工，导致成熟rRNA的形成受损，并因此抑制蛋白质合成，四环素类抗生素对此广为人知。由于rRNA的结构和加工途径在细菌物种之间是保守的，