Study of the role of Mg2+ in dsRNA processing mechanism by bacterial RNase III through QM/MM simulations

  • Salvador I. Drusin
  • Rodolfo M. Rasia
  • Diego M. MorenoEmail author
Original Paper


The ribonuclease III (RNase III) cleaves dsRNA in specific positions generating mature RNAs. RNase III enzymes play important roles in RNA processing, post-transcriptional gene expression, and defense against viral infection. The enzyme’s active site contains Mg2+ ions bound by a network of acidic residues and water molecules, but there is a lack of information about their specific roles. In this work, multiple steered molecular dynamics simulations at QM/MM level were performed to explore the hydrolysis reaction carried out by the enzyme. Free energy profiles modifying the features of the active site are obtained and the role of Mg2+ ions, the solvent molecules and the residues of the active site are discussed in detail. Our results show that Mg2+ ions carry out different roles in the hydrolysis process positioning the substrate for the attack from a coordinated nucleophile and activating it to perform hydrolysis reaction, cleaving the dsRNA backbone in a SN2 substitution. In addition, water molecules present in the active site lower the energy barrier of the process.

Graphical abstract

RNase III hydrolyzes dsRNA to generate mature RNAs. For this purpose, its active site contains Mg2+ which has an important role during the reaction. Results show that the Mg2+ activates the solvent molecule that produces the nucleophilic attack and the surrounding waters contribute significantly to the hydrolysis process.


RNase III QM/MM DFTB Reaction mechanism dsRNA 



This research was supported by grants from CONICET and Universidad Nacional de Rosario to D.M.M., S.I.D. has received a fellowship from CONICET. R.R. and D.M.M are members of CONICET. The result presented in this work were obtained using the resources of Centro de Cómputos de Alto Rendimiento (CeCAR), FCEN-UBA.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

775_2019_1741_MOESM1_ESM.pdf (558 kb)
Supplementary material 1 (PDF 558 kb)


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Copyright information

© Society for Biological Inorganic Chemistry (SBIC) 2019

Authors and Affiliations

  1. 1.Instituto de Biología Molecular y Celular de Rosario (CONICET-UNR)RosarioArgentina
  2. 2.Área Física, Departamento de Químico-Física, Facultad de Ciencias Bioquímicas y FarmacéuticasUniversidad Nacional de RosarioRosarioArgentina
  3. 3.Área Biofísica, Facultad de Ciencias Bioquímicas y FarmacéuticasUniversidad Nacional de RosarioRosarioArgentina
  4. 4.Instituto de Química de Rosario (CONICET-UNR)RosarioArgentina
  5. 5.Área Química General e Inorgánica, Departamento de Química-Física, Facultad de Ciencias Bioquímicas y FarmacéuticasUniversidad Nacional de RosarioRosarioArgentina

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