title: Single nucleotide polymorphism-specific regulation of matrix metalloproteinase-9 by multiple miRNAs targeting the coding exon.
abstract: Microribonucleic acids (miRNAs) work with exquisite specificity and are able to distinguish a target from a non-target based on a single nucleotide mismatch in the core nucleotide domain. We questioned whether miRNA regulation of gene expression could occur in a single nucleotide polymorphism (SNP)-specific manner, manifesting as a post-transcriptional control of expression of genetic polymorphisms. In our recent study of the functional consequences of matrix metalloproteinase (MMP)-9 SNPs, we discovered that expression of a coding exon SNP in the pro-domain of the protein resulted in a profound decrease in the secreted protein. This missense SNP results in the N38S amino acid change and a loss of an N-glycosylation site. A systematic study demonstrated that the loss of secreted protein was due not to the loss of an N-glycosylation site, but rather an SNP-specific targeting by miR-671-3p and miR-657. Bioinformatics analysis identified 41 SNP-specific miRNA targeting MMP-9 SNPs, mostly in the coding exon and an extension of the analysis to chromosome 20, where the MMP-9 gene is located, suggesting that SNP-specific miRNAs targeting the coding exon are prevalent. This selective post-transcriptional regulation of a target messenger RNA harboring genetic polymorphisms by miRNAs offers an SNP-dependent post-transcriptional regulatory mechanism, allowing for polymorphic-specific differential gene regulation.
authors.affiliation: Molecular and Cellular Pharmacology Graduate Program, University of Wisconsin, SMI 301, 1300 University Ave., Madison, WI 53706, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Duellman
authors.affiliation: Proteovista LLC, Madison, WI 53719, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Warren
authors.affiliation: Molecular and Cellular Pharmacology Graduate Program, University of Wisconsin, SMI 301, 1300 University Ave., Madison, WI 53706, USA Department of Anesthesiology, University of Wisconsin, Madison, WI 53706, USA Jyang75@wisc.edu.
authors.forename: Jay
authors.initials: J
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions; D000483:Alleles; D001483:Base Sequence; D001665:Binding Sites; D004794:Enzyme Repression; D005091:Exons; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D017422:Sequence Analysis, DNA
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9