title: Stability of miRNA 5'terminal and seed regions is correlated with experimentally observed miRNA-mediated silencing efficacy.
abstract: MicroRNAs (miRNAs) are key regulators of sequence-specific gene silencing. However, crucial factors that determine the efficacy of miRNA-mediated target gene silencing are poorly understood. Here we mathematized base-pairing stability and showed that miRNAs with an unstable 5' terminal duplex and stable seed-target duplex exhibit strong silencing activity. The results are consistent with the previous findings that an RNA strand with unstable 5' terminal in miRNA duplex easily loads onto the RNA-induced silencing complex (RISC), and miRNA recognizes target mRNAs with seed-complementary sequences to direct posttranscriptional repression. Our results suggested that both the unwinding and target recognition processes of miRNAs could be proficiently controlled by the thermodynamics of base-pairing in protein-free condition. Interestingly, such thermodynamic parameters might be evolutionarily well adapted to the body temperatures of various species.
authors.affiliation: Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo , 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba-ken 277-8561, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hibio
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Hino
authors.forename: Eigo
authors.initials: E
authors.lastname: Shimizu
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Nagata
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ui-Tei
mesh_terms: D000818:Animals; D001181:Arthropods; D020029:Base Pairing; D001483:Base Sequence; D001831:Body Temperature; D002645:Chickens; D030541:Databases, Genetic; D004285:Dogs; D020868:Gene Silencing; D017930:Genes, Reporter; D006367:HeLa Cells; D006736:Horses; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D035683:MicroRNAs; D034743:RNA-Induced Silencing Complex