title: General rules for functional microRNA targeting.
abstract: The functional rules for microRNA (miRNA) targeting remain controversial despite their biological importance because only a small fraction of distinct interactions, called site types, have been examined among an astronomical number of site types that can occur between miRNAs and their target mRNAs. To systematically discover functional site types and to evaluate the contradicting rules reported previously, we used large-scale transcriptome data and statistically examined whether each of approximately 2 billion site types is enriched in differentially downregulated mRNAs responding to overexpressed miRNAs. Accordingly, we identified seven non-canonical functional site types, most of which are novel, in addition to four canonical site types, while also removing numerous false positives reported by previous studies. Extensive experimental validation and significantly elevated 3' UTR sequence conservation indicate that these non-canonical site types may have biologically relevant roles. Our expanded catalog of functional site types suggests that the gene regulatory network controlled by miRNAs may be far more complex than currently understood.
authors: Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea.|School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Doyeon
authors: D
authors: Kim
authors: School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
authors: You Me
authors: YM
authors: Sung
authors: Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea.|School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Jinman
authors: J
authors: Park
authors: Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea.|School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Sukjun
authors: S
authors: Kim
authors: Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea.|School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Jongkyu
authors: J
authors: Kim
authors: School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Junhee
authors: J
authors: Park
authors: School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Haeok
authors: H
authors: Ha
authors: School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Jung Yoon
authors: JY
authors: Bae
authors: Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea.|School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
authors: SoHui
authors: S
authors: Kim
authors: Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea.|School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.|Bioinformatics Institute, Seoul National University, Seoul, Republic of Korea.
authors: Daehyun
authors: D
authors: Baek
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger