title: Sequence features associated with microRNA strand selection in humans and flies.
abstract: BACKGROUND
  During microRNA (miRNA) maturation in humans and flies, Drosha and Dicer cut the precursor transcript, thereby producing a short RNA duplex. One strand of this duplex becomes a functional component of the RNA-Induced Silencing Complex (RISC), while the other is eliminated. While thermodynamic asymmetry of the duplex ends appears to play a decisive role in the strand selection process, the details of the selection mechanism are not yet understood.
  
  
  RESULTS
  Here, we assess miRNA strand selection bias in humans and fruit flies by analyzing the sequence composition and relative expression levels of the two strands of the precursor duplex in these species. We find that the sequence elements associated with preferential miRNA strand selection and/or rejection differ between the two species. Further, we identify another feature that distinguishes human and fly miRNA processing machinery: the relative accuracy of the Drosha and Dicer enzymes.
  
  
  CONCLUSIONS
  Our result provides clues to the mechanistic aspects of miRNA strand selection in humans and other mammals. Further, it indicates that human and fly miRNA processing pathways are more distinct than currently recognized. Finally, the observed strand selection determinants are instrumental in the rational design of efficient miRNA-based expression regulators.
authors.affiliation: Partner Institute for Computational Biology, 320 Yue Yang Road, Shanghai, 200031, PR China. oceanhu@126.com
authors.forename: Hai Yang
authors.initials: HY
authors.lastname: Hu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Corinna
authors.initials: C
authors.lastname: Menzel
authors.forename: Yan Hong
authors.initials: YH
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Philipp
authors.initials: P
authors.lastname: Khaitovich
mesh_terms: D000465:Algorithms; D000818:Animals; D002874:Chromosome Mapping; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics*; D020869:Gene Expression Profiling; D015894:Genome, Human; D049750:Genome, Insect; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D020365:RNA Helicases / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D017423:Sequence Analysis, RNA / Q000379:methods*; D013045:Species Specificity
chemical_list: D029721:Drosophila Proteins; D035683:MicroRNAs; C515033:Dcr-1 protein, Drosophila; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; C493335:drosha protein, Drosophila; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases