Altered Gene Expression Associated with microRNA Binding Site Polymorphisms.
Allele-specific gene expression associated with genetic variation in regulatory regions can play an important role in the development of complex traits. We hypothesized that polymorphisms in microRNA (miRNA) response elements (MRE-SNPs) that either disrupt a miRNA binding site or create a new miRNA binding site can affect the allele-specific expression of target genes. By integrating public expression quantitative trait locus (eQTL) data, miRNA binding site predictions, small RNA sequencing, and Argonaute crosslinking immunoprecipitation (AGO-CLIP) datasets, we identified genetic variants that can affect gene expression by modulating miRNA binding efficiency. We also identified MRE-SNPs located in regions associated with complex traits, indicating possible causative mechanisms associated with these loci. The results of this study expand the current understanding of gene expression regulation and help to interpret the mechanisms underlying eQTL effects.
Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
Urmo
U
Võsa
Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia; Division of Endocrinology, Children's Hospital, Boston, MA, United States of America; Department of Genetics, Harvard Medical School, Boston, MA, United States of America; Broad Institute, Cambridge, MA, United States of America.
Tõnu
T
Esko
Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
Silva
S
Kasela
Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
Tarmo
T
Annilo
D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins; D015870:Gene Expression; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics; D015810:Linkage Disequilibrium; D035683:MicroRNAs / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D040641:Quantitative Trait Loci; D034622:RNA Interference
D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C506160:ISCU protein, human; D007506:Iron-Sulfur Proteins; C482775:MDM4 protein, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins