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Interaction of the tetracyclines with double-stranded RNAs of random base sequence: new perspectives on the target and mechanism of action.
J Antibiot (Tokyo). 2016 08; 69(8):622-30.JA

Abstract

The 16S rRNA binding mechanism proposed for the antibacterial action of the tetracyclines does not explain their mechanism of action against non-bacterial pathogens. In addition, several contradictory base pairs have been proposed as their binding sites on the 16S rRNA. This study investigated the binding of minocycline and doxycycline to short double-stranded RNAs (dsRNAs) of random base sequences. These tetracyclines caused a dose-dependent decrease in the fluorescence intensities of 6-carboxyfluorescein (FAM)-labelled dsRNA and ethidium bromide (EtBr)-stained dsRNA, indicating that both drugs bind to dsRNA of random base sequence in a manner that is competitive with the binding of EtBr and other nucleic acid ligands often used as stains. This effect was observable in the presence of Mg(2+). The binding of the tetracyclines to dsRNA changed features of the fluorescence emission spectra of the drugs and the CD spectra of the RNA, and inhibited RNase III cleavage of the dsRNA. These results indicate that the double-stranded structures of RNAs may have a more important role in their interaction with the tetracyclines than the specific base pairs, which had hitherto been the subject of much investigation. Given the diverse functions of cellular RNAs, the binding of the tetracyclines to their double-stranded helixes may alter the normal processing and functioning of the various biological processes they regulate. This could help to explain the wide range of action of the tetracyclines against various pathogens and disease conditions.

Authors+Show Affiliations

Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, London, UK. Department of Veterinary Pathology and Microbiology, University of Nigeria, Nsukka, Enugu State, Nigeria.Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, London, UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26786504

Citation

Chukwudi, Chinwe U., and Liam Good. "Interaction of the Tetracyclines With Double-stranded RNAs of Random Base Sequence: New Perspectives On the Target and Mechanism of Action." The Journal of Antibiotics, vol. 69, no. 8, 2016, pp. 622-30.
Chukwudi CU, Good L. Interaction of the tetracyclines with double-stranded RNAs of random base sequence: new perspectives on the target and mechanism of action. J Antibiot (Tokyo). 2016;69(8):622-30.
Chukwudi, C. U., & Good, L. (2016). Interaction of the tetracyclines with double-stranded RNAs of random base sequence: new perspectives on the target and mechanism of action. The Journal of Antibiotics, 69(8), 622-30. https://doi.org/10.1038/ja.2015.145
Chukwudi CU, Good L. Interaction of the Tetracyclines With Double-stranded RNAs of Random Base Sequence: New Perspectives On the Target and Mechanism of Action. J Antibiot (Tokyo). 2016;69(8):622-30. PubMed PMID: 26786504.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interaction of the tetracyclines with double-stranded RNAs of random base sequence: new perspectives on the target and mechanism of action. AU - Chukwudi,Chinwe U, AU - Good,Liam, Y1 - 2016/01/20/ PY - 2015/10/08/received PY - 2015/11/02/revised PY - 2015/12/08/accepted PY - 2016/1/21/entrez PY - 2016/1/21/pubmed PY - 2017/5/4/medline SP - 622 EP - 30 JF - The Journal of antibiotics JO - J Antibiot (Tokyo) VL - 69 IS - 8 N2 - The 16S rRNA binding mechanism proposed for the antibacterial action of the tetracyclines does not explain their mechanism of action against non-bacterial pathogens. In addition, several contradictory base pairs have been proposed as their binding sites on the 16S rRNA. This study investigated the binding of minocycline and doxycycline to short double-stranded RNAs (dsRNAs) of random base sequences. These tetracyclines caused a dose-dependent decrease in the fluorescence intensities of 6-carboxyfluorescein (FAM)-labelled dsRNA and ethidium bromide (EtBr)-stained dsRNA, indicating that both drugs bind to dsRNA of random base sequence in a manner that is competitive with the binding of EtBr and other nucleic acid ligands often used as stains. This effect was observable in the presence of Mg(2+). The binding of the tetracyclines to dsRNA changed features of the fluorescence emission spectra of the drugs and the CD spectra of the RNA, and inhibited RNase III cleavage of the dsRNA. These results indicate that the double-stranded structures of RNAs may have a more important role in their interaction with the tetracyclines than the specific base pairs, which had hitherto been the subject of much investigation. Given the diverse functions of cellular RNAs, the binding of the tetracyclines to their double-stranded helixes may alter the normal processing and functioning of the various biological processes they regulate. This could help to explain the wide range of action of the tetracyclines against various pathogens and disease conditions. SN - 1881-1469 UR - https://www.unboundmedicine.com/medline/citation/26786504/Interaction_of_the_tetracyclines_with_double_stranded_RNAs_of_random_base_sequence:_new_perspectives_on_the_target_and_mechanism_of_action_ DB - PRIME DP - Unbound Medicine ER -