A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes.
We present rna22, a method for identifying microRNA binding sites and their corresponding heteroduplexes. Rna22 does not rely upon cross-species conservation, is resilient to noise, and, unlike previous methods, it first finds putative microRNA binding sites in the sequence of interest, then identifies the targeting microRNA. Computationally, we show that rna22 identifies most of the currently known heteroduplexes. Experimentally, with luciferase assays, we demonstrate average repressions of 30% or more for 168 of 226 tested targets. The analysis suggests that some microRNAs may have as many as a few thousand targets, and that between 74% and 92% of the gene transcripts in four model genomes are likely under microRNA control through their untranslated and amino acid coding regions. We also extended the method's key idea to a low-error microRNA-precursor-discovery scheme; our studies suggest that the number of microRNA precursors in mammalian genomes likely ranges in the tens of thousands.
Miranda
Kevin C
KC
Bioinformatics and Pattern Discovery Group, IBM Thomas J. Watson Research Center, Yorktown Heights, P.O. Box 218, NY 10598, USA.
Huynh
Tien
T
Tay
Yvonne
Y
Ang
Yen-Sin
YS
Tam
Wai-Leong
WL
Thomson
Andrew M
AM
Lim
Bing
B
Rigoutsos
Isidore
I
D000465:Algorithms; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002107:Caenorhabditis / Q000235:genetics; D002460:Cell Line; D019295:Computational Biology / Q000379:methods; D004330:Drosophila / Q000235:genetics; D016678:Genome / Q000235:genetics; D020180:Heteroduplex Analysis / Q000379:methods*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008967:Molecular Biology / Q000379:methods; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics* / Q000378:metabolism*; D016366:Open Reading Frames / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012985:Software Design; D020506:Untranslated Regions / Q000235:genetics
D035683:MicroRNAs; D009692:Nucleic Acid Heteroduplexes; D012333:RNA, Messenger; D020506:Untranslated Regions