caa a22 4500 605511330 CHVBK 20210128100650.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00894-015-2760-8 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2760-8 Effect of mismatch on binding of ADAR2/GluR-2 pre-mRNA complex [Elektronische Daten] [Junru Yang, Jianing Song, John Zhang, Changge Ji] RNA editing plays an important role in realizing the full potential of a given genome. Different from RNA splicing, RNA editing fine-tunes the sequence of RNA by changing only one or two nucleotides. A-I editing [deamination of adenosine (A) to create inosine (I)] is best characterized in mammals and occurs in the regions of double-stranded RNA (dsRNA). Adenosine deaminases acting on RNA (ADARs) are members of a family of enzymes involved in A-I deamination editing in numerous mRNA and pre-mRNA transcripts. Experimental study shows that ADAR2 selectively edits the R/G site, while ADAR1 edits more promiscuously at several other adenosines. How ADAR2 selects specific sites for deamination is poorly understood. Mismatches have been suggested to be important factors that allow the ADAR2 to achieve specific deamination. Using molecular dynamic simulation, we studied the effect of mismatch on binding stability of the dsRNA/ADAR2 complex. By comparison of two binding domains of ADAR2, we found that ADAR2 dsRBM2 (second binding domain of ADAR2) does not bind well with mismatch reversed GluR-2 RNA. When mismatch is reversed, dsRBM2 of ADAR2 slides along the RNA duplex in the simulation. Detailed structural analysis indicates that the minor groove width of dsRNA and global shape of RNA may play an important role in the specific reading mechanism of ADAR2. Springer-Verlag Berlin Heidelberg, 2015 RNA editing nationallicence A-I deamination editing nationallicence Adenosine deaminases acting on RNA (ADARs) nationallicence GluR-2 pre-mRNA nationallicence Mismatch nationallicence MD simulation nationallicence Yang Junru Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 200062, Shanghai, China aut Song Jianing Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 200062, Shanghai, China aut Zhang John State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, 200062, Shanghai, China aut Ji Changge Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 200062, Shanghai, China aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/9(2015-09-01), 1-10 1610-2940 21:9<1 2015 21 894 https://doi.org/10.1007/s00894-015-2760-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2760-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yang Junru Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 200062, Shanghai, China aut NATIONALLICENCE 700 1- Song Jianing Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 200062, Shanghai, China aut NATIONALLICENCE 700 1- Zhang John State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, 200062, Shanghai, China aut NATIONALLICENCE 700 1- Ji Changge Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 200062, Shanghai, China aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/9(2015-09-01), 1-10 1610-2940 21:9<1 2015 21 894