title: Mutagen-specific mutation signature determines global microRNA binding.
abstract: Micro-RNAs (miRNAs) are small non-coding RNAs that regulate gene products at the post-transcriptional level. It is thought that loss of cell regulation by miRNAs supports cancer development. Based on whole genome sequencing of a melanoma tumor, we predict, using three different computational algorithms, that the melanoma somatic mutations globally reduce binding of miRNAs to the mutated 3'UTRs. This phenomenon reflects the nature of the characteristic UV-induced mutation, C-to-T. Furthermore, we show that seed regions are enriched with Guanine, thus rendering miRNAs prone to reduced binding to UV-mutated 3'UTRs. Accordingly, mutation patterns in non UV-induced malignancies e.g. lung cancer and leukemia do not yield similar predictions. It is suggested that UV-induced disruption of miRNA-mediated gene regulation plays a carcinogenic role. Remarkably, dark-skinned populations have significantly higher GC content in 3'UTR SNPs than light-skinned populations, which implies on evolutionary pressure to preserve regulation by trans-acting oligonucleotides under conditions with excess UV radiation.
authors.affiliation: Ella Institute of Melanoma, Sheba Medical Center, Ramat-Gan, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Greenberg
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.forename: Oz
authors.initials: O
authors.lastname: Solomon
authors.forename: Jacob
authors.initials: J
authors.lastname: Schachter
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
authors.forename: Eran
authors.initials: E
authors.lastname: Eyal
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000465:Algorithms; D001482:Base Composition / Q000235:genetics; D030541:Databases, Genetic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics* / Q000528:radiation effects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs
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