title: Sampling the structure of the noncanonical lin-4:lin-14 microRNA:mRNA complex by molecular dynamics simulations.
abstract: siRNA and microRNA (miRNA) are two classes of noncoding RNAs that carry out post-transcriptional gene regulation by interacting with the target mRNA. The structural features of siRNA/miRNA-mRNA complex play a crucial role in gene silencing. Here we have used computer modeling and simulation approach to (i) elucidate the possible structures of the partially complementary lin-4:lin-14 miRNA-mRNA complex and (ii) compare the structural features with the fully complementary lin-4:lin-14 siRNA-mRNA complex. The fully complementary siRNA complex maintains a canonical helical shape while the presence of mismatch base pairs and bulge induce a kinked structure in the miRNA complex. Docking of the simulated duplex models on to the argonaute protein gives a direct indication that in the siRNA-mRNA structure, the scissile phosphate of the mRNA strand is more accessible to the catalytic site as compared to the miRNA-mRNA structures, providing an explanation for the less prevalence of the cleavage in the later case.
authors.affiliation: Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi 110 007, India.
authors.forename: Chandramouli
authors.initials: C
authors.lastname: Balasubramanian
authors.forename: Rajendra Prasad
authors.initials: RP
authors.lastname: Ojha
authors.forename: Souvik
authors.initials: S
authors.lastname: Maiti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Desideri
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry; D035683:MicroRNAs / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry; D012333:RNA, Messenger / Q000737:chemistry*; D051880:Receptors, Notch
chemical_list: D029742:Caenorhabditis elegans Proteins; C102669:LIN-14 protein, C elegans; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch