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New class of microRNA targets containing simultaneous 5'-UTR and 3'-UTR interaction sites

 Inhan Lee  ;  Subramanian S. Ajay  ;  Jong In Yook  ;  Hyun Sil Kim  ;  Su Hyung Hong  ;  Nam Hee Kim  ;  Saravana M. Dhanasekaran  ;  Arul M. Chinnaiyan  ;  Brian D. Athey 
 GENOME RESEARCH, Vol.19(7) : 1175-1183, 2009 
Journal Title
Issue Date
3' Untranslated Regions/genetics ; 3' Untranslated Regions/metabolism* ; 5' Untranslated Regions/physiology* ; Axin Protein ; Base Sequence ; Blotting, Western ; Cell Culture Techniques ; Cytoskeletal Proteins/genetics ; Cytoskeletal Proteins/metabolism* ; Humans ; Kidney/embryology ; MicroRNAs/genetics* ; Molecular Sequence Data ; RNA, Messenger/antagonists & inhibitors ; RNA, Messenger/genetics* ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Nucleic Acid ; Transfection ; Wnt1 Protein/genetics ; Wnt1 Protein/metabolism*
MicroRNAs (miRNAs) are known to post-transcriptionally regulate target mRNAs through the 3'-UTR, which interacts mainly with the 5'-end of miRNA in animals. Here we identify many endogenous motifs within human 5'-UTRs specific to the 3'-ends of miRNAs. The 3'-end of conserved miRNAs in particular has significant interaction sites in the human-enriched, less conserved 5'-UTR miRNA motifs, while human-specific miRNAs have significant interaction sites only in the conserved 5'-UTR motifs, implying both miRNA and 5'-UTR are actively evolving in response to each other. Additionally, many miRNAs with their 3'-end interaction sites in the 5'-UTRs turn out to simultaneously contain 5'-end interaction sites in the 3'-UTRs. Based on these findings we demonstrate combinatory interactions between a single miRNA and both end regions of an mRNA using model systems. We further show that genes exhibiting large-scale protein changes due to miRNA overexpression or deletion contain both UTR interaction sites predicted. We provide the predicted targets of this new miRNA target class, miBridge, as an efficient way to screen potential targets, especially for nonconserved miRNAs, since the target search space is reduced by an order of magnitude compared with the 3'-UTR alone. Efficacy is confirmed by showing SEC24D regulation with hsa-miR-605, a miRNA identified only in primate, opening the door to the study of nonconserved miRNAs. Finally, miRNAs (and associated proteins) involved in this new targeting class may prevent 40S ribosome scanning through the 5'-UTR and keep it from reaching the start-codon, preventing 60S association.
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2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
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