Potent effect of target structure on microRNA function.
MicroRNAs (miRNAs) are small noncoding RNAs that repress protein synthesis by binding to target messenger RNAs. We investigated the effect of target secondary structure on the efficacy of repression by miRNAs. Using structures predicted by the Sfold program, we model the interaction between an miRNA and a target as a two-step hybridization reaction: nucleation at an accessible target site followed by hybrid elongation to disrupt local target secondary structure and form the complete miRNA-target duplex. This model accurately accounts for the sensitivity to repression by let-7 of various mutant forms of the Caenorhabditis elegans lin-41 3' untranslated region and for other experimentally tested miRNA-target interactions in C. elegans and Drosophila melanogaster. These findings indicate a potent effect of target structure on target recognition by miRNAs and establish a structure-based framework for genome-wide identification of animal miRNA targets.
Long
Dang
D
Wadsworth Center, New York State Department of Health, 150 New Scotland Avenue, Albany, New York 12208, USA.
Lee
Rosalind
R
Williams
Peter
P
Chan
Chi Yu
CY
Ambros
Victor
V
Ding
Ye
Y
D020413:3' Untranslated Regions / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D009711:Nucleotides / Q000378:metabolism; D018510:RNA, Helminth / Q000737:chemistry* / Q000235:genetics; D012044:Regression Analysis; D012984:Software; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014157:Transcription Factors / Q000378:metabolism
D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; C410586:LIN-41 protein, C elegans; D035683:MicroRNAs; D050505:Mutant Proteins; D009711:Nucleotides; D018510:RNA, Helminth; D014157:Transcription Factors; C474488:let-7 microRNA, C elegans