Sequence features associated with microRNA strand selection in humans and flies.
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.
Hu
Hai Yang
HY
Partner Institute for Computational Biology, 320 Yue Yang Road, Shanghai, 200031, PR China. oceanhu@126.com
Yan
Zheng
Z
Xu
Ying
Y
Hu
Hao
H
Menzel
Corinna
C
Zhou
Yan Hong
YH
Chen
Wei
W
Khaitovich
Philipp
P
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
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